Systems for genome selection

ABSTRACT

Systems, methods, compositions and apparatus relating to genome selection are disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to and claims the benefit of theearliest available effective filing date(s) from the following listedapplication(s) (the “Related Applications”) (e.g., claims earliestavailable priority dates for other than provisional patent applicationsor claims benefits under 35 USC §119(e) for provisional patentapplications, for any and all parent, grandparent, great-grandparent,etc. applications of the Related Application(s)).

RELATED APPLICATIONS

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 11/651,447, entitled SYSTEMS FOR GENOME SELECTION,naming W. Daniel Hillis, Roderick A. Hyde, Edward K. Y. Jung, RobertLanger, Nathan P. Myhrvold and Lowell L. Wood, Jr. as inventors, filed 8Jan. 2007, which is currently co-pending, or is an application of whicha currently co-pending application is entitled to the benefit of thefiling date.

The United States Patent Office (USPTO) has published a notice to theeffect that the USPTO's computer programs require that patent applicantsreference both a serial number and indicate whether an application is acontinuation or continuation-in-part. Stephen G. Kunin, Benefit ofPrior-Filed Application, USPTO Official Gazette Mar. 18, 2003, availableat http://www.uspto.gov/web/offices/com/sol/og/2003/week11/patbene.htm.The present Applicant Entity (hereinafter “Applicant”) has providedabove a specific reference to the application(s) from which priority isbeing claimed as recited by statute. Applicant understands that thestatute is unambiguous in its specific reference language and does notrequire either a serial number or any characterization, such as“continuation” or “continuation-in-part,” for claiming priority to U.S.patent applications. Notwithstanding the foregoing, Applicantunderstands that the USPTO's computer programs have certain data entryrequirements, and hence Applicant is designating the present applicationas a continuation-in-part of its parent applications as set forth above,but expressly points out that such designations are not to be construedin any way as any type of commentary and/or admission as to whether ornot the present application contains any new matter in addition to thematter of its parent application(s).

All subject matter of the Related Applications and of any and allparent, grandparent, great-grandparent, etc. applications of the RelatedApplications is incorporated herein by reference to the extent suchsubject matter is not inconsistent herewith.

SUMMARY

The present application relates, in general, to methods of selectinggerm line genomes at least partially based on one or more geneticcharacteristics of the germ line genomes and related systemsimplementations, apparatus and/or compositions. Such methods, systems,apparatus, and/or compositions are useful for selecting and/oridentifying germ line genomes optionally for use in fertilization. Germline genomes may be selected to include certain target geneticcharacteristics and/or to exclude certain target characteristics asoptionally determined by a systems operator. Illustrative examplesinclude selection of germ lines that exclude certain geneticcharacteristics linked with disease risk, and/or that include certaingenetic characteristics linked with milk production or egg laying.

Various methods for selecting one or more germ line genomes aredisclosed, including but not limited to, various methods for selectingmale germ line genomes and/or female germ line genomes. Methods forselecting male germ line genomes include, but are not limited to,hybridization-based selection methods, female geneticcharacteristics-based selection methods, chromatin decondensation-basedselection methods, and/or spermatid subtractive determination-basedselection methods. Methods for selecting female germ line genomesinclude, but are not limited to, male genetic characteristics-basedselection methods and/or polar body subtractive determination-basedselection methods.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1, FIG. 2, and FIG. 3 show operational flows representingillustrative embodiments of operations related to determining parametersfor selecting one or more reproductive components based on a firstpossible dataset.

FIG. 4 shows optional embodiments of the operational flow of FIG. 1,FIG. 2, and/or FIG. 3.

FIG. 5 shows optional embodiments of the operational flow of FIG. 1,FIG. 2, and/or FIG. 3.

FIG. 6 shows optional embodiments of the operational flow of FIG. 1,FIG. 2, and/or FIG. 3.

FIG. 7 shows optional embodiments of the operational flow of FIG. 1,FIG. 2, and/or FIG. 3.

FIG. 8 shows optional embodiments of the operational flow of FIG. 1,FIG. 2, and/or FIG. 3.

FIG. 9 shows optional embodiments of the operational flow of FIG. 1,FIG. 2, and/or FIG. 3.

FIG. 10 shows optional embodiments of the operational flow of FIG. 1,FIG. 2, and/or FIG. 3.

FIG. 11, FIG. 12, and FIG. 13 show partial views of an illustrativeembodiment of a computer program product that includes a computerprogram for executing a computer process on a computing device.

FIG. 14 shows an illustrative embodiment of a system in whichembodiments may be implemented.

FIG. 15 shows a schematic of an illustrative apparatus in whichembodiments may be implemented.

FIG. 16 shows schematics of illustrative embodiments of the apparatus ofFIG. 15, with illustrative examples of a sourcing unit.

FIG. 17 shows schematics of illustrative embodiments of the apparatus ofFIG. 15, with specific examples of a hybridization unit.

FIG. 18 shows schematics of illustrative embodiments of the apparatus ofFIG. 15, with illustrative examples of a monitoring unit.

FIG. 19 shows schematics of illustrative embodiments of the apparatus ofFIG. 15, with illustrative examples of a controller unit.

FIG. 20 shows schematics of illustrative embodiments of the apparatus ofFIG. 15, with illustrative examples of a computing unit.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here.

The present application relates, in general, to systems, apparatus,compositions, and methods of selecting germ line genomes. Those havingskill in the art will appreciate that the specific systems, apparatus,compositions, and methods described herein are intended as merelyillustrative of their more general counterparts.

As used herein, the term “germ line” means germ cells having geneticmaterial that may be passed to offspring. Germ cells include, but arenot limited to, gametogonia (e.g. spermatogonia and oogonia),gametocytes (e.g. spermatocytes and oocytes) and gametes (e.g.spermatozoa and ova).

As used herein, the term “haploid germ line” means germ cells having oneset of the genetic material that may be passed to offspring. Haploidgerm cells include, but are not limited to, second polar bodies, ova,secondary spermatocytes, spermatids, and spermatozoa.

As used herein, the term “genome(s)” means the hereditary information ofan organism typically encoded in nucleic acids, either DNA, or RNA, andincluding both genes and non-coding sequences. The genome may refer tothe nucleic acids making up one set of chromosomes of an organism(haploid genome) or both sets of chromosomes of an organism (diploidgenome) depending on the context in which it is used. The genome mayalso include, or be limited to, a mitochondrial genome or a chloroplastgenome, for example, depending on the context. The genome may be atleast partially isolated, part of a nucleus, and/or in a cell, such asbut not limited to, a germ cell or a somatic cell. In some embodiments,one or more genomes may include, but not be limited to, nuclear,organellar, chloroplast and/or mitochondrial genomes.

As used herein, the term “genetic characteristic(s)” means anymeasurable, detectable, and/or identifiable element encoded by,associated with, correlated with, and/or linked to one or more nucleicacid sequences, chromosomal structures, or genomic determinants. Thecharacteristic or element may include, but not be limited to, one ormore of a repeat sequence, an inversion, an insertion, a deletion, asubstitution, a duplication, a cross-over, a recombination, a SNP, ahaplotype, a centromere sequence, a methylation pattern, an epigeneticelement, an intron, an exon, a regulatory sequence, an intergenicsequence, and/or a coding or non-coding sequence of nucleotides. Thecharacteristic or element may also include, but not be limited to,allelic markers, alleles, disease markers, genetic abnormalities,genetic diseases, chromosomal abnormalities, genetic mutations and/orprotein coding sequences. The characteristic or element may alsoinclude, but not be limited to, aspects of mitochondrial nucleic acidsequences and mitochondria. The characteristic or element may alsoinclude, but not be limited to, aspects of telomeres including, but notlimited to, telomere sequence, telomere repeats and telomere lengths.The characteristic or element may include, but not be limited to, one ormore of one or more physical attributes, mental attributes, intellectualattributes, or psychological attributes, or a combination thereof.

As used herein, the term “physical attributes” means any measurable,detectable, and/or identifiable characteristic that may be seen,touched, heard, smelled, or felt or that is involved in one of theseprocesses and is encoded by, associated with, correlated with, and/orlinked to one or more nucleic acid sequences, chromosomal structures, orgenomic determinants. Examples include, but are not limited to,characteristics associated with height, disease state, body type, hipdysplasia, vision, strength, flexibility, speed, coordination, gait,foot color, lactation, fertility, weight, pelt, skin, skeleto-muscular,longevity, hair, eyes, fur, fleece, wool, hair pattern, hair color, eyecolor, eye sight, bone length, bone density, skin color, fur thickness,fur color, fur texture (e.g. rough, smooth, thin, thick), fleece color,fleece thickness, wool thickness, and wool color.

As used herein the term “mental attributes” means any measurable,detectable, and/or identifiable characteristics related to thefunctioning of the mind encoded by, associated with, correlated with,and/or linked to one or more nucleic acid sequences, chromosomalstructures, or genomic determinants. Mental attributes may include, butare not limited to intellectual attributes and psychological attributes.Examples include, but are not limited to, intelligence, disposition,mental disorders, depression, insanity, persistence and self-confidence.

The genetic basis for physiology, biochemistry, disease, physicaltraits, mental traits, intellectual traits, and/or psychological traitsof biological entities is known in the art. The genetic basis isdetermined optionally through associations, correlations and/or linkagesamong one or more genetic characteristics (Ciba Found. Symp. (1987)130:215-228). Genetic determinants may be dominant, recessive, partial,and/or multi-factorial. In some embodiments, homozygous alleles may beselected and/or heterozygous alleles may be selected. Additional geneticassociations are identifiable using the techniques described in thereferenced art.

Illustrative examples of genetic associations, correlations, and/orlinkages include, but are not limited to, genetic mechanisms of disease(Nat. Clin. Prat. Rheumatol. (2006) 2:671-678; Curr. Pharm. Des. (2006)12:3753-3759; Semin. Oncol. (2006) 33:544-551; J. Alzheimers Dis. (2006)9:45-52; Hum. Mol. Genet. (2006) 15:R117-23; Front. Biosci. (2007)12:1563-1573; Am. J. Pharmacogenomics (2005) 5:71-92; Front. Biosci.(2007) 12:2670-2682; Autoimmunity (2006) 39:433-444; Nat. Clin. Pract.Endocrinol. Metab. (2006) 2:282-290; Immunogenetics (2006) 58:347-354;BMC Genomics (2006) 7:65; Nat. Rev. Genet. (2006) 7:306-318; Gynecol.Endocrinol. (2006) 22:18-24; Joint Bone Spine (2005) 72:520-526; J.Hypertension (2005) 23:2127-2143; Clin. Sci. (London) (2005)109:355-364; Front. Biosci. (2006) 11:570-580; Periodontol. 2000 (2005)39:91-117; Philos. Trans. R. Soc. Lond. B. Biol. Sci. (2005)360:1529-36), molecular determinants of brain size (Biochem. Biophys.Res. Commun. (2006) 345:911-916), genetic influences on cognition(Philos. Trans. R. Soc. Lond. B. Biol. Sci. (2006) 361:2129-2141; GenesBrain Behavior (2006) 5:44-53; Ment. Retard Dev. Disabil. Res. Rev.(2005) 11:279-285), genetic basis for sleep regulation (Semin. Neurol.(2006) 26:467-483), genetic influences on behavior (Am. J. Psychiatry(2006) 163:1683-1694), genetics of speech (J. Neuroscience (2006)26:10376-10379); genetic associations for personality (Biol. Psychiatry(2006) October 24; Eur. Neuropsychopharmacol. (2006) August 7; GenesBrain Behav. (2006) 5:240-248); and genetic relationship to athleticperformance (Respir. Physiol. Neurobiol. (2006) 151:109-123; Hum. Genet.(2005) 116:331-339; Med. Sci. Sports Exerc. (2006) 38:1863-1888; PLoSGenet. (2005) 1:e42). Illustrative examples of genetic basis forsusceptibility and/or resistance for disease include but are not limitedto genetic determinants or predispositions for Tay-Sachs disease andsickle cell disease (optionally heterozygous alleles are preferred), aswell as modified T cell receptors associated with protection from HIVinfection.

As used herein, the term “reference genetic characteristic” means agenetic characteristic that is used as a comparator. Optionally, thecomparator can be neutral, desirable, or not desirable. A referencegenetic characteristic may be selected for or selected against.

As used herein, the term “target genetic characteristic” means a geneticcharacteristic that is used as a goal. A target genetic characteristicmay be determined by comparison with reference genetic characteristics,for example. A target genetic characteristic may be selected for orselected against, unless context dictates otherwise.

As used herein, the term “weighted analysis” means according one or moretarget traits and/or genetic characteristics greater, equal or lesserweight based on identifiable criteria. Weighting may be objective,subjective, programmable, and/or user defined.

As used herein, the term “single nucleotide polymorphism(s) or SNP(s)”means a nucleic acid sequence variation occurring when a singlenucleotide—A, T, C, or G—in the genome (or other shared sequence)differs between members of a species (or between paired chromosomes inan individual). Within a population, SNPs can be assigned a minor allelefrequency, the ratio of chromosomes in the population carrying the lesscommon variant to those with the more common variant. SNPs with a minorallele frequency of ≧1% occur every 100 to 300 bases along the humangenome, on average, where two of every three SNPs substitute cytosinewith thymine. SNPs may fall within coding sequences of genes, noncodingregions of genes, or in the intergenic regions between genes. A SNPwithin a coding region, in which both forms lead to the same proteinsequence, is termed synonymous; if different proteins are produced theyare non-synonymous. SNPs that are not in protein coding regions may haveconsequences for gene splicing, transcription factor binding, or thesequence of non-coding RNA, for example, and/or may indicate thehaplotype of the organism.

As used herein, the term “haplotype” means the genetic make up ofnucleic acid such as, but not limited to, an individual chromosome, achromatid, a locus, or an entire genome. In the case of diploidorganisms, a genome-wide haplotype comprises one member of the pair ofalleles for each locus (that is, half of a diploid genome). A haplotyperefers to a set of SNPs on a chromatid that are statisticallyassociated. These associations, and the identification of a few allelesof a haplotype block, can identify other polymorphic sites in itsregion. Methods for determining haplotypes are known in the art andinclude, but are not limited to, fluorescent in situ hybridization(FISH) referenced herein.

As used herein, the term “chromosomal characteristic(s)” means normaland abnormal features of chromosomes. Chromosomal characteristicsinclude, but are not limited to, ploidy, translocations, insertions,deletions, rearrangements, and/or mutations. Chromosomal aberrations arefrequently associated with lethality and genetic disorders. The numbersof known associations have increased dramatically with the advent of theHuman Genomes Project, and have lead to extensive web-based informationon genetic disorders. Methods for detecting chromosomal characteristicsare known in the art and described herein.

As used herein, the term “nucleic acid(s)” means one or more complex,high-molecular-weight biochemical macromolecules composed of nucleotidechains. Nucleic acids include, but are not limited to, one or more formsof deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acidsequence(s) refers the order of the nucleotides along one or morenucleic acid strands. Methods of determining nucleic acid sequencesincluding target nucleic acid sequences are known in the art. In someembodiments, one or more nucleic acid sequences include, but are notlimited to, those that encode one or more proteins, are transcribed intoone or more RNA (including, but not limited to, rRNA, tRNA and/orsiRNA), are regulatory sequences or repeating sequences, and/or have anat least partially undefined/unknown role. In some embodiments, one ormore nucleic acid sequences include, but are not limited to, introns,exons, junk DNA, telomeres and centromeres, pseudogenes and/or hot-spotsfor duplication of DNA regions.

As used herein, the term “chromatin” means a complex of DNA and proteintypically found, for example, inside the nuclei of eukaryotic cells. Thenucleic acids are generally in the form of double-stranded DNA exceptfor some germ line cells, or undergoing meiosis or mitosis. In somaticcells and some, but not all, germ line cells, the major proteinsinvolved in chromatin are histones. In some germ line cells, includingbut not limited to, spermatozoa and some spermatids, the major proteinsinvolved in chromatin are protamines.

As used herein, the term “condensed chromatin” means the more tightlypackaged DNA/protein complex that occurs to varying extents duringvarious stages of mitosis & meiosis, for example. During spermiogenesis,spermatid chromatin is remodeled into a more tightly packaged structurewhere histones are partially or mostly displaced, and partially orcompletely replaced by protamines (small, arginine-rich proteins). As aresult, some but not all spermatids, as well as spermatozoa, havepartially or completely condensed chromatin.

As used herein, the term “condensed, decondensation, and/orrecondensation” refers to protamine-based condensation of chromatinunless context dictates otherwise.

As used herein, the term “polyamide” means a molecule, optionally apolymer, containing one or more units, each one optionally a monomer,joined by peptide bonds. The units are optionally natural and/ornon-natural amino acids. Although not intended to be limiting,polyamides are understood to bind to nucleic acids, such as DNA, suchthat the double helix is not disrupted, apparently by binding to theminor or major groove of the double helix.

As used herein, the term “protein nucleic acid” means a nucleic acidwith a backbone composed of repeating N-(2-aminoethyl)-glycine unitslinked by peptide bonds. The various purine and pyrimidine bases arelinked to the backbone by methylene carbonyl bonds. PNA binds to DNA bydisplacing one of the strands and forming Watson-Crick base pairs withthe other strand. PNA also binds to RNA by Watson-Crick base pairs.

As used herein, the term “related spermatids” means one or more of thefour spermatids that arise during meiosis of a spermatogonium throughfirst and second spermatocytes. The four spermatids that are generatedfrom a single spermatogonium are “related” as used herein. The haplotypeof one or more of the related spermatids may be partially and/orcompletely determined by knowing the haplotype of a relatedspermatogonium (or any related diploid cell) and the haplotypes of oneor more of the other related spermatids. The haplotype of one of therelated spermatids may be completely determined by knowing the haplotypeof a related spermatogonium (or any related diploid cell) and thehaplotypes of the other three related spermatids.

As used herein, the term “related polar bodies” means one or more of thefirst and second polar bodies that arise during meiosis of a primaryoocyte. The three polar bodies that arise from single primary oocyte are“related” as used herein. The haplotypes of one or more of the relatedpolar bodies and/or related ovum can be determined by knowing thehaplotype of the primary oocyte (or any related diploid cell) and one ormore of the polar body ovum haplotypes. The “related ovum” is the ovumarising from the primary oocyte term which the related polar bodiesarose.

As used herein, the term “related female germ line genomes” means afemale germ line genome that arises during meiosis of a primary oocyte.Related female germ line genomes include secondary oocytes, ova, andpolar bodies, including first polar bodies and second polar bodies.

As used herein, the term “related diploid cell” means a diploid germline or somatic cell from the same biological entity as a relatedspermatid or a related polar body.

As used herein, the term “at least partially” means partially orcompletely. “Completely” means as completely as reasonably possiblescientifically and/or economically. “Partially” means anything less thancompletely, but more than not at all. Partially includes, but is notlimited to 99%, 98%, 97%, 96%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%,55%, 40%, 30%, 25%, 15%, 10%, 5%, 4%, 3%, 2%, and/or 1%. Partiallyincludes, but is not limited to, 1-99, 5-99, 10-99, 25-99, 40-99, 60-99,80-99, 5-90, 5-75, 5-55, 5-30, 5-15, 5-10, 25-95, 25-85, 25-65, 25-45,60-90, 60-75, 40-65, and/or 15-35 percent.

As used herein, the term “biological entity” means one or more livingentities including, but not limited to, plants, animals, microorganisms,prokaryotes, eukaryotes, protozoa, bacteria, mammals, yeast, E. coli,humans, reptile, insect, bird, amphibian, and/or fish. The animals mayinclude, but are not limited to, domesticated, wild, research, zoo,sports, pet, primate, marine, and/or farm animals. Animals include, butare not limited to, bovine, porcine, swine, ovine, murine, canine,avian, feline, equine, and/or rodent animals. Domesticated and/or farmanimals include, but are not limited to, chickens, horses, cattle, pigs,sheep, donkeys, mules, rabbits, goats, ducks, geese, chickens, and/orturkeys. Wild animals include, but are not limited to, non-humanprimates, bear, deer, elk, raccoons, squirrels, wolves, coyotes,opossums, foxes, skunks, and/or cougars. Research animals include, butare not limited to, rats, mice, hamsters, guinea pigs, rabbits, pigs,dogs, cats and/or non-human primates. Pets include, but are not limitedto, dogs, cats, gerbils, hamsters, guinea pigs and/or rabbits. Reptilesinclude, but are not limited to, snakes, lizards, alligators,crocodiles, iguanas, and/or turtles. Avian animals include, but are notlimited to, chickens, ducks, geese, owls, sea gulls, eagles, hawks,and/or falcons. Fish include, but are not limited to, farm-raised, wild,pelagic, coastal, sport, commercial, fresh water, salt water, and/ortropical. Marine animals include, but are not limited to, whales,sharks, seals, sea lions, walruses, penguins, dolphins, and/or fish. Oneor more of the genomes described herein may be part of or included inone or more biological entities.

As used herein, the term “identifying” means one or more process used todetermine one or more components, wherein the one or more componentsoptionally include, but are not limited to, one or more genomes, one ormore germ line genomes, one or more chromosomal characteristics, one ormore genetic characteristics, one or more single nucleotidepolymorphisms, one or more haplotypes, one or more nucleic acidsequences, one or more genomes, one or more germ line cells, one or morenuclei, etc. and/or other “items” that are appropriate when read in thecontext in which they occur in the description. Processes include, butare not limited to, user selected, user identified, user determined,software method analysis, algorithm-based, computer mediated, operationsresearch, optimization, simulation, queuing theory, and/or game theory.Illustrative embodiments of such processes include but are not limitedto information processing, information technology, datamining, and/ordatabase analysis.

As used herein, the term “separating” means one or more process used topartially or completely isolate from one another one or more components,and/or one or more process that result in one or more components beingno longer located in the same place. The one or more componentsoptionally include, but are not limited to, one or more genomes, one ormore germ line cells, one or more nuclei, etc. and/or other componentsthat are appropriate when read in the context in which they occur in thedescription. Processes include, but are not limited to, manual,automatic, semi-automatic, remote-controlled, and/or robotic.Illustrative embodiments of such processes include but are not limitedto fluorescence activated cell sorting (FACS).

As used herein, the term “selecting” means one or more process used to“identify” and/or “separate” one or more components, optionally one ormore reproductive components, optionally one or more germ line genomes,optionally one or more genetic characteristics. The one or morecomponents optionally include, but are not limited to, one or morechromosomal characteristics, one or more genetic characteristics, one ormore single nucleotide polymorphisms, one or more haplotypes, one ormore nucleic acid sequences, one or more genomes, one or more germ linecells, one or more nuclei, etc. and/or other “items” that areappropriate when read in the context in which they occur in thedescription. Processes include, but are not limited to, those describedabove for “identifying” and/or “separating”.

As used herein, the term “selecting for . . . based on” and “selectingagainst . . . based on” means one or more process used to “identify” and“separate” one or more components, optionally one or more reproductivecomponents, and/or optionally one or more germ line genomes, using (orbased on) defined parameters. Using (based on) defined parameters mayinclude detecting the presence and/or absence of one or more geneticcharacteristics, and/or the presence or absence of a weightedcombination of one or more genetic characteristics, for example. Using(based on) defined parameters may include detecting the increase and/ordecrease of one or more genetic characteristics, and/or the increase ordecrease of a weighted combination of one or more geneticcharacteristics, for example.

As used herein, “presence and/or absence” means detectable and/or notdetectable based on scientific and/or economic reasonableness. Somethingmay be detectable and/or undetectable scientifically if a signal isabove background and/or below background using a scientificallyappropriate assay, and/or if a signal is altered, for example increasedand/or decreased, in a statistically significant manner.

As used herein, the term “increase and/or decrease” means a change oralteration (up or down as scientifically appropriate) in the level ofdetectability as compared with a control and/or reference level,optionally a statistically significant change in the level ofdetectability as compared with a control and/or reference level.

As used herein, the term “providing and/or co-localizing” means anyprocess resulting in one or more components being in the same place atthe same time. By “in the same place at the same time” is meant physicalproximity such that the one or more components are capable ofinteraction on a molecular level. Providing may include, co-localizing,comingling, combining, mixing, assembling, aggregating, injecting, orother similar processes. Methods for providing molecules to the nucleusof living cells are known in the art and include, but are not limitedto, microinjection, scrape-loading, bead-loading, osmotic lysis ofpinosomes, liposome transfection, and cell permeablization (Journal ofCell Science (1987) 88:669-678; Methods (2003) 29:51-57).

Generic processes useful for co-localizing, providing and/or separating,and including sequential processes, are known in the art and include,but are not limited to, one or more of manual methods, automated orsemi-automated methods, robot-controlled methods, remote-controlledmethods, mechanical methods, electrical methods, computer and/orsoftware-controlled methods, and fluid flow. Fluid flow includes, but isnot limited to, nanofluidics and microfluidics. Nanofluidics andmicrofluidics include, but are not limited to, continuous flowmicrofluidics and digital microfluidics, and have been developed for usein biological systems (Annu. Rev. Fluid Mech. (2004) 36:381-411; Annu.Rev. Biomed. Eng. (2002) 4:261-86; Science (1988) 242:1162-1164, Rev.Mod. Phys. (2005) 77:977-1026).

As used herein, the term “hybridization” means one or more processes forco-localizing complementary, single-stranded nucleic acids, and/orco-localizing complementary non-traditional molecules with single- ordouble-stranded nucleic acids through strand separation andre-annealing, for example. In illustrative embodiments, complementaryPNA and/or nucleic acid molecules, optionally oligonucleotides, mayhybridize to single- or double-stranded DNA.

Methods for hybridization are known in the art, and include, but are notlimited to, conditions for low and high stringency hybridization(Sambrook and Russell. (2001) Molecular Cloning: A Laboratory Manual 3rdedition. Cold Spring Harbor Laboratory Press; Sambrook, Fritsch,Maniatis. Molecular Cloning: A Laboratory Manual 3^(rd) edition.includes a spiral bound, 3 volume set, associated with a web site as anon-line laboratory manual (www.MolecularCloning.com)). Stringency of thehybridization may be controlled (e.g. by the washing conditions) torequire up to 100% complementarity between the probe and the targetsequence (high stringency), or to allow some mismatches between theprobe and the target sequence (low stringency). Factors to determine theappropriate hybridization and wash conditions based on the target andthe probe are known in the art. In illustrative embodiments, followingthe first wash using 0.2×SSC/0.1% SDS for 10 minutes at 68° C., twoadditional washes with 0.2×SSC/0.1% SDS for 15 minutes each at 68° C.are performed for high stringency washes, two additional washes at0.2×SSC/0.1% SDS for 15 minutes each at 42° C. for moderate stringencywashes, and two additional washes 0.2×SSC/0.1% SDS for 15 minutes eachat room temperature for low stringency washes.

As used herein, the term “genotyping” means one or more processes fordetermining the genotype of one or more biological entities. Methods ofgenotyping include, but are not limited to, PCR, DNA sequencing, andhybridization to DNA chips or beads. In illustrative embodiments, notintended to be in any way limiting, short tandem repeats, microsatelliteDNA, mitochondrial DNA, and/or single nucleotide polymorphisms may beused for genotyping (Forensic Sci. Int. (2004) 146 suppl:S171-3;Forensic Sci. Int. (2005) 50:519-525; Forensic Sci. Int. (2005)153:237-246; Forensic Sci. Int. (2005) 153:247-259; Forensic Sci. Int.(2005) 154:111-121; Forensic Sci. Int. (2005) 154:181-194; Forensic Sci.Int. (2005) 154:128-136; Forensic Sci. Int. (2006) 157:23-35; Int. J.Legal Med. (2005) 119:10-15; Methods Mol. Biol. (2005) 297:229-242;Electrophoresis (2005) 26:4411-4420; Leg. Med. (Tokyo) (2005)7:259-262).

As used herein, the term “detecting” means one or more processes formeasuring and/or identifying and/or documenting and/or recording thepresence or absence and/or amount and/or type and/or intensity of acharacteristic, for example, or as appropriate in the context usedherein. Methods for detecting molecular genetic alterations are known inthe art. Methods include those appropriate for viable or living cellsand/or non-viable or non-living cells.

Sequences that include only one base pair change or single nucleotidepolymorphism (SNP) can be detected using one or more methods describedherein, and/or methods known in the art. Methods for detecting singlenucleic acid transcripts, SNPs, and chromosomal abnormalities are knownin the art and include, but are not limited to a variety of FISH andother fluorescent techniques (Science (1998) 280:585-590; BioTechniques(2006) 40:489-495). Methods for detecting large scale geneticalterations such as, but not limited to, allelic imbalance,microsatellite instability, insertions, deletions, translocations, andaberrant methylation are known in the art and include, but are notlimited to, digital SNP analysis (Clinical Cancer Research (2002)8:2580-2585).

Methods for detecting specific nucleic acid sequences in viable and/ornon-viable cells and/or nuclei are known in the art and include, but arenot limited to, using labeled oligonucleotides, labeled protein nucleicacid (PNA) oligonucleotides, and labeled polyamides (Current OrganicChemistry (2006) 10:491-518; Mol. Hum. Reprod. (2004) 10:467-472;Mammalian Genome (2000) 11:384-391; Adv. in Genetics (2006) 56:1-51; TheEMBO Journal (2003) 22: 6631-6641; Eur. J. Hum. Genetics (2003)11:337-341; Mammalian Genome (1999) 10: 13-18; The EMBO Journal (2001)20:3218-3228; Bioorganic & Medicinal Chem. Lett. (2003) 13:1565-1570;Nuc. Acids Res. (2004) 32:2802-2818; Thesis by T. P. Best (2005)California Institute of Technology; Methods (2003) 29:51-57). Quenchedprobes, such as molecular beacons and quenched auto-ligation probes,provide highly specific detection of nucleic acids, for example (Trendsin Biotech. (2005) 23:225-230). Although in some instances, one or moremethods are described for RNA, they can be used analogously for DNA.

Methods for imaging nucleic acid molecules, including single nucleicacid molecules, within living cells and/or living cell nuclei are knownin the art, and include, but are not limited to, ultra-sensitive opticaltechniques for imaging fluorescent probes and/or quantum dots (Biochem.Biophys. Res. Commun. (2006) 344:772-779; Histochem. Cell Biol. (2006)125:451-456; Trends in Cell Biol. (1998) 8:288292; Biophys. J. (2000)78:2170-2179; Anal. Chem. (2000) 72:5606-5611; Nature (2004) 5:856-862;Science (2004) 304:1797-1800; Biomedical Optics (2005) 10:051406-1 to051406-9). Although in some instances one or more methods are describedfor one type of nucleic acid, they can be used analogously for othertypes of nucleic acid.

As used herein, the term “decondensing” means one or more processes fordecreasing and/or reversing the condensation of one or more nucleicacids with proteins, and including for example, but not limited to,decreasing the condensation of chromatin including one or morechromosomes, one or more portions of chromosomes, one or more genomes,or one or more portions of genomes. As used herein, the term “condensingand/or re-condensing” means one or more processes for increasingcondensation and/or reversing the decondensation of one or more nucleicacids with proteins including, but not limited to, protamines andoptionally histones, and including for example, but not limited to,increasing the condensation of chromatin including one or morechromosomes, one or more portions of chromosomes, one or more genomes,or one or more portions of genomes. In some embodiments, the termsdecondensing/recondensing apply specifically to chromatin of spermatids,spermatocytes, and/or spermatozoa that has been partially or completelycondensed and/or decondensed in association with protamines andoptionally histones.

Methods for decondensing chromatin of spermatids, spermatocytes, and/orspermatozoa that have been partially or completely condensed inassociation with protamines are known in the art. Methods may bedestructive and/or non-destructive of the cells, genomes, and/or nuclei,and may result in viable or non-viable genomes. Methods for partialand/or complete decondensation include, but are not limited to, exposureto dithiothreitol, glutathione, heparin, and/or heparin sulfate, andsimilar reagents, and one or more of these treatments render sperm stillfunctional for fertilization (J. Cell Science (2005) 118:1811-1820; Hum.Repro. (2005) 20:2784-2789; Theriogenology (2005) 63:783-794; J. Exp.Zool. (1999) 284:789-797; J. Biol. Chem. (2004) 279:20088-20095).Methods for partial and/or complete decondensation of one or morepartially and/or completely condensed genomes include exposure toextracts from stimulated ova, exposure to stimulated ova, and/orexposure to recombinant and/or reconstituted extracts of stimulated ova.By stimulated is meant the changes that occur during fertilization.

Methods for identifying genetic characteristics in condensed, partiallycondensed, partially decondensed, and/or partially recondensed male germline haploid genomes are known in the art, and non-random chromosomepositioning in sperm has been established (J. Cell Science (2005)118:1811-1820; Biol. Repro. (1993) 48:1193-1201; J. Cell Science (2005)118:4541-4550).

As used herein, the term “fertilizing” means co-localizing two genomesin a first location such that the genomes form at least one diploidgenome including genetic information from both genomes with thepotential to become a viable biological entity and/or with the potentialto initiate development and/or is totitpotent. In some embodiments, atleast one genome is a haploid genome. In some embodiments, both genomesare haploid genomes. In some embodiments, at least one genome is adiploid genome. In some embodiments, one or more of the genomes are germline genomes. In some embodiments, at least one genome is a male germline genome. In some embodiments, at least one genome is a female germline genome.

Methods for fertilization are known in the art and include, but are notlimited to, intracytoplasmic injection of mature and/or immature,damaged and/or undamaged, sperm cells, nuclei, and/or genomes,including, for example, ICSI (Hum. Repro. (2002) 4:990-998; Hum. Repro.(1998) 13:117-127; Reproduction (2005) 130:907-916; Mol. Repro. & Devel.(2004) 68:96-102; Theriogenology (2005) 63:783-794).

As used herein, the term “in vitro” means performing a given action incells or parts of cells in a controlled environment outside a livingbiological entity. In vitro actions may be destructive, non-destructive,at least partially destructive, or at least partially non-destructive.

As used herein, the term “destructive” means damaging to the cell orpart of a cell such that it no longer is able to be used in the methodsdescribed herein, such as selecting, separating, or sorting genomes, andoptionally fertilization. Unless contrary to a given context, the termdestructive may refer to damage to a cell or part of a cell that thatresults in a partial or complete loss of viability.

As used herein, the term “non-destructive” means limiting damage to thecell or part of a cell such that it is able to be used in the methodsdescribed herein, such as selecting, separating, or sorting genomes, andoptionally fertilization. Unless contrary to a given context, the termnon-destructive may refer to damage to a cell or part of a cell thatthat results in partial or no loss of viability.

In one aspect, the disclosure is drawn to one or more methods forselecting one or more germ line genomes at least partially based on oneor more genetic characteristics of one or more germ line genomes.Although one or more methods may be presented separately herein, it isintended and envisioned that one or more methods and/or embodiments ofone or more methods may be combined and/or substituted to encompass thefull disclosure. In some embodiments, one or more methods describedherein are used to generate one or more compositions described herein,and/or are performed on one or more apparatus described herein. In someembodiments, one or more methods may include one or more operations, andusing all or more computing devices and/or systems.

In some embodiments, one or more methods include hybridizing one or moreprobes in vitro to one or more nucleic acid sequences of one or moremale germ line haploid genomes; determining one or more geneticcharacteristics of the one or more male germ line haploid genomes; andselecting one or more of the one or more male germ line haploid genomesbased at least partially on one or more of the one or more geneticcharacteristics of the one or more male germ line haploid genomes.

In some embodiments, one or more methods include detecting one or moregenetic characteristics of one or more male germ line haploid genomes atleast partially based on methods other than binding of one or morenucleic acids of the one or more male germ line haploid genomes with apolyamide or Hoechst; and selecting one or more of the one or more malegerm line haploid genomes based at least partially on the one or moregenetic characteristics of the one or more male germ line haploidgenomes. In some embodiments, the one or more probes do not include apolyamide.

In some embodiments, one or more methods include detecting one or moregenetic characteristics of one or more male germ line haploid genomes atleast partially based on sequence-specific binding to one or morenucleic acids of the one or more male germ line haploid genomes, andselecting one or more of the one or more male germ line haploid genomesbased at least partially on the one or more genetic characteristics ofthe one or more male germ line haploid genomes.

In some embodiments, one or more methods include detecting one or moregenetic characteristics of one or more male germ line haploid genomes atleast partially based on using one or more probes containing one or morenucleic acid elements, and selecting one or more of the one or more malegerm line haploid genomes based at least partially on the one or moregenetic characteristics of the one or more male germ line haploidgenomes.

In some embodiments, one or more methods include detecting one or moregenetic characteristics of one or more male germ line haploid genomes atleast partially based on using one or more probes that do not bind tothe minor groove of DNA, and selecting one or more of the one or moremale germ line haploid genomes based at least partially on the one ormore genetic characteristics of the one or more male germ line haploidgenomes.

In some embodiments, one or more methods include detecting one or moregenetic characteristics of one or more male germ line haploid genomes atleast partially based on using one or more probes that bind to the majorgroove of DNA, and selecting one or more of the one or more male germline haploid genomes based at least partially on the one or more geneticcharacteristics of the one or more male germ line haploid genomes.

In some embodiments, one or more methods include hybridizing one or morenucleic acid sequence specific probes in vitro to the one or morenucleic acid sequences of the one or more male germ line haploidgenomes. In some embodiments, one or more of the one or more probes areselected from the group consisting of a protein nucleic acid and anoligonucleotide.

In some embodiments, one or more methods include determining one or moregenetic characteristics of the one or more male germ line haploidgenomes at least partially based on detecting the hybridization of theone or more probes in vitro to the one or more nucleic acid sequences ofthe one or more male germ line haploid genomes.

In some embodiments, one or more methods further include detecting thehybridization of the one or more probes in vitro to the one or morenucleic acid sequences of the one or more male germ line haploidgenomes. In some embodiments, detecting the hybridization of the one ormore probes in vitro is at least partially based on the presence of adetectable marker of hybridization, the detectable marker ofhybridization is optionally selected from the group consisting ofquantum dots, molecular beacons, and fluorescence, including but notlimited to, fluorescence resonance energy transfer (FRET), andfluorescence in situ hybridization (FISH).

In some embodiments, one or more methods further include analyzing oneor more genetic characteristics of the one or more male germ linehaploid genomes. In some embodiments, analyzing one or more geneticcharacteristics includes, but is not limited to, comparing one or moregenetic characteristics of one or more male germ line haploid genomeswith one or more reference and/or one or more target geneticcharacteristics. In some embodiments, analyzing one or more geneticcharacteristics includes, but is not limited to, performing a weightedanalysis of one or more of the one or more male germ line haploidgenomes at least partially based on a comparison with one or morereference genetic characteristics and/or one or more target geneticcharacteristics.

In some embodiments, one or more methods include selecting for oragainst one or more reference and/or one or more target geneticcharacteristics, and/or a weighted combination of one or more referenceand/or one or more target genetic characteristics.

In some embodiments, analyzing one or more genetic characteristics ofone or more male germ line haploid genomes includes analyzing optionallya weighted combination of one or more of one or more single nucleotidepolymorphisms, one or more chromosomes, or one or more nucleic acidsequences of the one or more male germ line haploid genomes. In someembodiments, one or more methods include determining and/or selectingone or more reference genetic characteristics and/or the one or moretarget genetic characteristics at least partially based on one or moregenetic characteristics of one or more female germ line genomes.

In some embodiments, one or more methods include removing, separating,and/or eliminating one or more of the one or more probes from the one ormore male germ line haploid genomes and/or from one or more of the oneor more nucleic acid sequences of the one or more male germ line haploidgenomes.

In some embodiments, one or more male germ line haploid genomes are atleast partially condensed, are part of one or more spermatozoa, and/orare at least partially isolated from one or more spermatozoa. In someembodiments, one or more male germ line haploid genomes are part of oneor more spermatids, and/or are at least partially isolated from one ormore spermatids.

In some embodiments, one or more genetic characteristics of one or moremale germ line haploid genomes include a weighted combination of one ormore of the one or more genetic characteristics. In some embodiments,one or more genetic characteristics of the one or more male germ linehaploid genomes include one or more single nucleotide polymorphisms, oneor more chromosomal characteristics, one or more methylation patterns,one or more DNA sequences, one or more mitochondrial nucleic acidsequences, one or more telomeric sequences, and/or one or more telomericlengths, optionally selected from the group consisting of total genomictelomeric length, telomeric length of one or more ends of one or morechromosomes, and weighted combinations of one or more telomeric lengthsof one or more chromosomes.

In some embodiments, one or more SNPs may identify one or morehaplotypes to be selected for or selected against. In some embodiments,the one or more SNPs may alter one or more of one or more codingregions, one or more gene products, one or more non-coding regions, oneor more intergenic regions, one or more centromeric regions, one or moretelomeric regions, or one or more RNA In some embodiments, the one ormore SNPs may be in linkage disequilibrium with one or more traits, oneor more alleles, or one or more markers of chromosomal characteristics.

In some embodiments, one or more chromosomal characteristics mayinclude, but are not limited to, one or more duplications, insertions,deletions, substitutions, replications or breaks. In some embodiments,the one or more duplications are of one or more chromosomes (forexample, trisomy 21) and/or of portions of one or more chromosomes. Insome embodiments, one or more chromosomal characteristics may include,but are not limited to, haplotype and/or nucleic acid sequence.

In some embodiments, one or more nucleic acid sequences may include, butare not limited to, repetitive sequences, telomeric sequences,centromeric sequences, mutated sequences, alternate sequences,intergenic sequences, protein coding sequences, and/or non-codingsequences. In some embodiments, the nucleic acid sequence may be linkedwith one or more disease or disorder, and optionally may encode a genelinked with one or more disease or disorder.

In some embodiments, one or more methods include selecting, sorting,and/or separating one or more of the one or more male germ line haploidgenomes based at least partially on one or more target geneticcharacteristics.

In some embodiments, one or more methods include selecting, sorting,and/or separating one or more of the one or more male germ line haploidgenomes based at least partially on one or more genetic characteristicsof one or more female germ line genomes.

In some embodiments, one or more methods include selecting, sorting,and/or separating one or more male germ line haploid genomes based atleast partially on one or more genetic characteristics of the one ormore male germ line haploid genomes; and wherein at least one of the oneor more genetic characteristics of the one or more male germ linehaploid genomes is selected, sorted and/or separated at least partiallybased on one or more genetic characteristics of one or more femalegenomes, optionally one or more female germ line genomes, optionally oneor more female germ line haploid genomes. In some embodiments, one ormore methods include determining one or more genetic characteristics ofone or more female genomes, optionally one or more female germ linegenomes, optionally one or more female germ line haploid genomes; andselecting, separating, and/or sorting one or more male germ line haploidgenomes at least partially based on the one or more geneticcharacteristics of the one or more female germ line genomes, optionallyone or more female germ line haploid genomes.

In illustrative embodiments, determining one or more geneticcharacteristics of one or more female germ line genomes includes, but isnot limited to, receiving an input including data representative of theone or more genetic characteristics of the one or more female germ linegenomes, where the input may be sent from an external or an internalsource. In some illustrative embodiments, the data representative of theone or more genetic characteristics of the one or more female germ linegenomes is generated internally. In illustrative embodiments,determining one or more genetic characteristics of one or more femalegerm line genomes includes, but is not limited to, co-localizing,binding, and/or hybridizing one or more probes and/or one or moremolecular markers with one or more nucleic acids of the one or morefemale germ line genomes.

In some embodiments, the one or more genetic characteristics of the oneor more male germ line haploid genomes and/or the one or more femalegerm line genomes include one or more single nucleotide polymorphisms,one or more chromosomal characteristics, one or more methylationpatterns, and/or one or more nucleic acid sequences; or a weightedcombination thereof. In some embodiments, one or more geneticcharacteristics of one or more male germ line haploid genomes and/orfemale germ line genomes include one or more mitochondrial nucleic acidsequences, one or more telomeric sequences, and/or one or more telomericlengths, or a weighted combination thereof. The one or more telomericlengths are optionally selected from the group consisting of a totalgenomic telomeric length, a telomeric length of one or more ends of oneor more chromosomes, and a weighted combination of one or more telomericlengths of one or more chromosomes.

In some embodiments, one or more SNPs may identify one or morehaplotypes to be selected for or selected against. In some embodiments,the one or more SNPs may alter one or more of one or more codingregions, one or more gene products, one or more non-coding regions, oneor more intergenic regions, one or more centromeric regions, one or moretelomeric regions, or one or more RNA In some embodiments, the one ormore SNPs may be in linkage disequilibrium with one or more traits, oneor more alleles, or one or more markers of chromosomal characteristics.

In some embodiments, one or more chromosomal characteristics mayinclude, but are not limited to, one or more duplications, insertions,deletions, substitutions, replications or breaks. In some embodiments,the one or more duplications are of one or more chromosomes (forexample, trisomy 21) and/or of portions of one or more chromosomes. Insome embodiments, one or more chromosomal characteristics may include,but are not limited to, haplotype and/or nucleic acid sequence.

In some embodiments, one or more nucleic acid sequences may include, butare not limited to, repetitive sequences, telomeric sequences,centromeric sequences, mutated sequences, alternate sequences,intergenic sequences, protein coding sequences, and/or non-codingsequences. In some embodiments, the nucleic acid sequence may be linkedwith one or more disease or disorder, and optionally may encode a genelinked with one or more disease or disorder.

In some embodiments, the one or more genetic characteristics of one ormore male germ line haploid genomes and/or one or more female germ linegenomes include a weighted combination of the one or more geneticcharacteristics, optionally including a weighted combination of one ormore of one or more single nucleotide polymorphisms, one or morechromosomal characteristics, one or more methylation patterns and/or oneor more nucleic acid sequences.

In some embodiments, one or more methods include using the selected oneor more male germ line haploid genomes to fertilize one or more eggscontaining one or more female germ line genomes. In some embodiments,one or more methods include providing and/or co-localizing the selectedone or more male germ line haploid genomes to and/or with the one ormore female germ line genomes. In some embodiments, the one or morefemale germ line genomes are one or more haploid genomes.

In some embodiments, one or more methods further include determining theone or more genetic characteristics of the one or more male germ linehaploid genomes and/or the one or more female germ line genomes. In someembodiments, determining the one or more genetic characteristics of theone or more genomes includes detecting one or more nucleic acidsequences of the one or more genomes optionally using one or morepolyamides and/or one or more protein nucleic acids.

In some embodiments, determining the one or more genetic characteristicsof the one or more male germ line haploid genomes and/or the one or morefemale germ line genomes includes co-localizing, optionally binding,optionally hybridizing, optionally in vitro, one or more probes and/orone or more molecular markers to one or more nucleic acid sequences ofone or more of the one or more genomes. In some embodiments, the one ormore probes are one or more nucleic acid specific probes, optionallyselected from the group consisting of oligonucleotide, protein nucleicacid, and polyamide.

In some embodiments, determining one or more of the one or more geneticcharacteristics of the one or more male germ line haploid genomes and/orone or more female germ line genomes is at least partially based ondetecting the association, optionally the binding, optionally thehybridization, of the one or more probes and/or one or more molecularmarkers with the one or more nucleic acid sequences of the one or moregenomes.

In some embodiments, one or more methods includes detecting theassociation, binding, and/or hybridization of the one or more probesand/or one or more molecular markers to the one or more nucleic acidsequences of the one or more male germ line haploid genomes and/or oneor more female germ line genomes, optionally by detecting theassociation, binding, and/or hybridization of the one or more probesbased on the presence of a detectable marker of hybridization, thedetectable marker of hybridization selected from the group consisting ofquantum dots, molecular beacons, and fluorescence, including FRET and/orFISH.

In some embodiments, one or more methods include separating the selectedone or more male germ line haploid genomes. In some embodiments, one ormore methods include using the selected one or more male germ linehaploid genomes to fertilize at least one of the one or more female germline genomes. In some embodiments, one or more methods include providingand/or co-localizing the selected one or more male germ line haploidgenomes to and/or with at least one of the one or more female germ linegenomes.

In some embodiments, one or more methods further include analyzing theone or more genetic characteristics of one or more male germ linehaploid genomes and/or one or more female germ line genomes. In someembodiments, analyzing one or more genetic characteristics of one ormore genomes comprises comparing one or more genetic characteristics ofthe one or more genomes with one or more reference geneticcharacteristics and/or target genetic characteristics. In someembodiments, one or more methods include determining, and/or selecting,one or more of the one or more reference genetic characteristics or theone or more target genetic characteristics at least partially based onone or more genetic characteristics of one or more female germ linegenomes and/or male germ line genomes. In some embodiments, the one ormore reference genetic characteristics and/or target geneticcharacteristics, and/or a weighted combination thereof, may be selectedfor or selected against. In some embodiments, analyzing the one or moregenetic characteristics of the one or more genomes comprises analyzingone or more single nucleotide polymorphisms, one or more chromosomes,one or more methylation patterns and/or one or more nucleic acidsequences of the one or more genomes.

In some embodiments, the one or more male germ line haploid genomes arepart of one or more spermatids, spermatocytes, or spermatozoa. In someembodiments, the one or more male germ line haploid genomes are isolatedfrom one or more spermatids, spermatocytes, or spermatozoa. In someembodiments, the one or more male germ line haploid genomes are at leastpartially condensed. In some embodiments, the one or more male germ linehaploid genomes are from one or more biological entities.

In some embodiments, the one or more female germ line genomes are partof and/or at least partially isolated from one or more of polar bodies,oogonia, or ova. In some embodiments, the one or more female germ linegenomes are from one or more biological entities.

In some embodiments, one or more methods include decondensing one ormore male germ line haploid genomes; determining one or more geneticcharacteristics of the one or more male germ line haploid genomes; andselecting, separating, and/or sorting one or more of the one or moremale germ line haploid genomes based at least partially on the one ormore genetic characteristics of the one or more male germ line haploidgenomes.

In some embodiments, one or more male germ line haploid genomes are partof one or more condensed spermatocytes or one or more spermatozoa,and/or are at least partially isolated from one or more condensedspermatocytes or one or more spermatozoa. In some embodiments, one ormore male germ line haploid genomes are from one or more biologicalentities.

In some embodiments, one or more methods include at least partiallydecondensing one or more male germ line haploid genomes. In someembodiments, one or more methods include decondensing in vitro one ormore of the one or more male germ line haploid genomes, optionally byproviding one or more reducing agents. In some embodiments, one or moremethods include providing one or more reducing agents to one or more ofthe one or more male germ line haploid genomes. In some embodiments, oneor more methods include providing one or more molecular markers to oneor more of the one or more male germ line haploid genomes, optionally toone or more decondensed male germ line haploid genomes.

In some embodiments, determining one or more genetic characteristics ofthe one or more male germ line haploid genomes includes co-localizing,binding, and/or hybridizing, optionally in vitro, one or more,optionally nucleic acid specific, probes and/or with one or more nucleicacid sequences of one or more male germ line haploid genomes.

In some embodiments, determining one or more genetic characteristics ofthe one or more male germ line haploid genomes includes detecting one ormore nucleic acid sequences of the one or more male germ line haploidgenomes. In some embodiments, detecting one or more nucleic acidsequences of the one or more male germ line haploid genomes includesdetecting one or more molecular markers and/or probes of the one or morenucleic acid sequences of the one or more male germ line haploidgenomes. In some embodiments, the one or more molecular markers and/orprobes are associated with, bound, and/or hybridized to the one or morenucleic acid sequences of the one or more male germ line haploidgenomes.

In some embodiments, determining one or more genetic characteristics ofthe one or more male germ line haploid genomes includes receiving datarepresentative of the one or more genetic characteristics and/or one ormore nucleic acid sequences of the one or more male germ line haploidgenomes. Insane embodiments, receiving data may be from an internaland/or an external source and/or input. In some embodiments, determiningone or more genetic characteristics of the one or more male germ linehaploid genomes includes analyzing the one or more geneticcharacteristics of the one or more male germ line haploid genomes.

In some embodiments, one or more methods include co-localizing, binding,and/or hybridizing one or more molecular markers and/or probes with oneor more nucleic acid sequences of the one or more male germ line haploidgenomes.

In some embodiments, one or more methods include detecting one or morenucleic acid sequences of the one or more male germ line haploidgenomes.

In some embodiments, one or more methods include analyzing the one ormore genetic characteristics of the one or more male germ line haploidgenomes. In some embodiments, analyzing the one or more geneticcharacteristics of the one or more male germ line haploid genomesincludes analyzing one or more single nucleotide polymorphisms, one ormore chromosomes, one or more methylation patterns, and/or one or morenucleic acid sequences of the one or more male germ line haploidgenomes.

In some embodiments, analyzing the one or more genetic characteristicsof the one or more male germ line haploid genomes includes comparing theone or more genetic characteristics of one or more male germ linehaploid genomes with, optionally a weighted combination of, one or morereference genetic characteristics and/or one or more target geneticcharacteristics. In some embodiments, the method includes selecting forone or more male germ line haploid genomes with one or more referencegenetic characteristics and/or the one or more target geneticcharacteristics and/or with a weighted combination of one or morereference genetic characteristics and/or one or more target geneticcharacteristics. In some embodiments, the method includes selectingagainst one or more male germ line haploid genomes with one or morereference genetic characteristics and/or the one or more target geneticcharacteristics and/or with a weighted combination of one or morereference genetic characteristics and/or one or more target geneticcharacteristics.

In some embodiments, one or more methods further include determiningand/or selecting one or more reference genetic characteristics and/orthe one or more target genetic characteristics at least partially basedon one or more genetic characteristics of one or more female germ linegenomes. In some embodiments, selecting one or more male germ linehaploid genomes includes selecting one or more male germ line haploidgenomes at least partially based on one or more genetic characteristicsof one or more female germ line genomes.

In some embodiments, one or more methods include separating and/orsorting the selected one or more male germ line haploid genomes. In someembodiments, one or more methods include providing and/or co-localizingthe one or more male haploid genomes with one or more female germ linegenomes.

In some embodiments, one or more methods include determining one or moregenetic characteristics of one or more related spermatid genomes; andselecting, separating, and/or sorting one or more related spermatidgenomes based at least partially on one or more genetic characteristicsof one or more related spermatid genomes.

In some embodiments, one or more related spermatid genomes are from oneor more biological entities. In some embodiments, one or more relatedspermatid genomes are at least partially isolated from one or morespermatids, and/or are part of one or more spermatids.

In some embodiments, determining one or more genetic characteristics ofone or more related spermatid genomes includes subtractively determiningone or more genetic characteristics of one or more related spermatidgenomes. In some embodiments, subtractively determining one or moregenetic characteristics of one or more related spermatid genomesincludes determining one or more genetic characteristics of one, two, orthree of the one or more related spermatid genomes; and comparing one ormore genetic characteristics of one, two, or three of the one or morerelated spermatid genomes with one or more genetic characteristics of arelated diploid genome.

In illustrative embodiments, one or more methods include determining oneor more genetic characteristics of one or more related spermatids bydetermining one or more genetic characteristics of three of the relatedspermatids, and through a comparative process, determining the one ormore genetic characteristics of the fourth related spermatid. In someillustrative embodiments, the comparative process is a subtractiveprocess, where the one or more genetic characteristics of the threerelated spermatids are compared with the one or more geneticcharacteristics of the related diploid genomes. The geneticcharacteristics of the related diploid genomes may be known, or may bedetermined by sequencing and/or haplotyping, for example.

In some embodiments, determining one or more genetic characteristics ofone or more related spermatid genomes includes determining, optionallydestructively, one or more genetic characteristics of one or morerelated diploid genomes, optionally of three related spermatid genomes,optionally of two related spermatid genomes, and/or optionally of onerelated spermatid genome.

In some embodiments, determining one or more genetic characteristics ofone or more related spermatid genomes includes amplifying, optionallydestructively, one or more nucleic acid sequences of the one or morerelated spermatid genomes and/or one or more related diploid genomes. Insome embodiments, amplifying one or more nucleic acid sequences of theone or more related spermatid genomes includes amplifying in vitro or insitu the one or more nucleic acid sequences of the one or more relatedspermatid genomes.

In some embodiments, determining one or more genetic characteristics ofone or more related spermatid genomes includes sequencing, optionallydestructively, one or more nucleic acids of one or more related diploidgenomes and/or one or more related spermatid genomes. In someembodiments, sequencing one or more nucleic acids of the one or morerelated spermatid genomes includes sequencing in vitro or in situ theone or more nucleic acids of the one or more related spermatid genomes.

In some embodiments, determining one or more genetic characteristics ofone or more related spermatid genomes includes co-localizing, binding,and/or hybridizing, optionally destructively, one or more probes and/orone or more molecular markers, optionally nucleic acid sequence specificprobes, to one or more nucleic acid sequences of the one or more relatedspermatid genomes. In some embodiments, co-localizing, binding, and/orhybridizing one or more probes and/or one or more molecular markers toone or more nucleic acid sequences of the one or more related spermatidgenomes includes co-localizing, binding, and/or hybridizing one or moreprobes and/or one or more molecular markers in vitro or in situ to theone or more nucleic acid sequences of the one or more related spermatidgenomes.

In some embodiments, determining the one or more genetic characteristicsof the one or more related spermatid genomes includes detecting and/oridentifying one or more nucleic acid sequences of the one or morerelated spermatid genomes. In some embodiments, detecting and/oridentifying one or more nucleic acid sequences of the one or morerelated spermatid genomes includes detecting and/or identifying one ormore markers of the one or more nucleic acid sequences of the one ormore related spermatid genomes, detecting and/or identifying one or moreprobes associated, bound, and/or hybridized to the one or more nucleicacid sequences of the one or more related spermatid genomes.

In some embodiments, determining one or more genetic characteristics ofone or more related spermatid genomes includes receiving datarepresentative of the one or more genetic characteristics of the one ormore related spermatid genomes and/or one or more related diploidgenomes. In some embodiments, receiving data representative of the oneor more genetic characteristics of the one or more related spermatidgenomes and/or one or more related diploid genomes includes receivingdata representative of one or more nucleic acid sequences of the one ormore related spermatid genomes and/or one or more related diploidgenomes. In some embodiments, receiving data may include receiving datafrom one or more internal and/or external sources and/or inputs.

In some embodiments, determining one or more genetic characteristics ofone or more related spermatid genomes includes analyzing the one or moregenetic characteristics of the one or more related spermatid genomesand/or one or more related diploid genomes.

In some embodiments, one or more methods include sequencing one or morenucleic acids of the one or more related spermatid genomes and/or one ormore related diploid genomes. In some embodiments, one or more methodsinclude co-localizing, binding, and/or hybridizing one or more molecularmarkers and/or one or more probes with one or more nucleic acidsequences of the one or more related spermatid genomes and/or one ormore related diploid genomes. In some embodiments, one or more methodsinclude detecting and/or identifying one or more nucleic acid sequencesof the one or more related spermatid genomes and/or one or more relateddiploid genomes.

In some embodiments, one or more methods include analyzing the one ormore genetic characteristics of the one or more related spermatidgenomes and/or one or more related diploid genomes. In some embodiments,analyzing the one or more genetic characteristics of the one or morerelated spermatid genomes includes analyzing one or more singlenucleotide polymorphisms, one or more chromosomes, one or moremethylation patterns, and/or one or more nucleic acid sequences of theone or more related spermatid genomes and/or one or more related diploidgenomes.

In some embodiments, determining one or more genetic characteristics ofone or more related spermatid genomes at least partially based on theone or more genetic characteristics of one or more related spermatidgenomes includes deducing and/or identifying the one or more geneticcharacteristics of the one or more related spermatid genomes at leastpartially based on the one or more genetic characteristics of one ormore of the one or more related spermatid genomes and/or one or morerelated diploid genomes.

In some embodiments, analyzing the one or more genetic characteristicsof the one or more related spermatid genomes includes comparing the oneor more genetic characteristics of the one or more related spermatidgenomes with one or more reference genetic characteristics and/or one ormore target genetic characteristics, and/or with a weighted combinationof one or more reference genetic characteristics and/or one or moretarget genetic characteristics. In some embodiments, one or more methodsinclude determining and/or selecting one or more reference geneticcharacteristics and/or the one or more target genetic characteristics atleast partially based on one or more genetic characteristics of one ormore female genomes optionally one or more female germ line genomes,and/or one or more male genomes, optionally are or more male germ linegenomes.

In some embodiments, comparing the one or more genetic characteristicsof the one or more related spermatid genomes with one or more referencegenetic characteristics and/or one or more target geneticcharacteristics includes selecting for and/or against one or morerelated spermatid genomes at least partially based on the presence ofone or more reference genetic characteristics and/or one or more targetgenetic characteristics, and/or the presence of a weighted combinationof one or more reference genetic characteristics and/or one or moretarget genetic characteristics.

In some embodiments, selecting one or more related spermatid genomesincludes selecting, sorting, and/or separating one or more relatedspermatid genomes at least partially based on one or more geneticcharacteristics of one or more female germ line genomes. In someembodiments, selecting one or more related spermatid genomes at leastpartially based on one or more genetic characteristics of one or morefemale germ line genomes includes selecting for and/or against one ormore of the one or more related spermatid genomes at least partiallybased on one or more genetic characteristics of one or more female germline genomes.

In some embodiments, one or more methods further include separatingand/or sorting the selected one or more related spermatid genomes. Insome embodiments, one or more methods further include co-localizingand/or providing one or more of the one or more related spermatidgenomes with one or more female germ line genomes.

In some embodiments, one or more methods include determining one or moregenetic characteristics of one or more related polar body genomes; andselecting, sorting, and/or separating one or more related female germline genomes based at least partially on the one or more geneticcharacteristics of the one or more related polar body genomes.

In some embodiments, one or more related polar body genomes and/or oneor more related female germ line genomes are from one or more biologicalentities. In some embodiments, one or more related polar body genomesare at least partially isolated from one or more polar bodies and/or arepart of one or more polar bodies. In some embodiments, one or morerelated polar body genomes are one or more first polar body genomesand/or one or more second polar body genomes.

In some embodiments, one or more related female germ line genomes are atleast partially isolated from one or more cells and/or are part of oneor more cells. In some embodiments, one or more of the one or morerelated female germ line genomes are at least partially isolated fromone or more ova, and/or are part of one or more ova. In someembodiments, one or more related female germ line genomes are at leastpartially isolated from one or more related polar bodies and/or are partof one or more related polar bodies.

In some embodiments, one or more methods further include determining oneor more genetic characteristics of one or more related female germ linegenomes. In some embodiments, determining one or more geneticcharacteristics of one or more related female germ line genomesincludes, but is not limited to, determining one or more geneticcharacteristics of one or more related polar body genomes. In someembodiments, determining one or more genetic characteristics of one ormore related female germ line genomes includes, but is not limited to,subtractively determining one or more genetic characteristics of one ormore related female germ line genomes. In some embodiments,subtractively determining one or more genetic characteristics of one ormore related female germ line genomes includes, but is not limited to,determining one or more genetic characteristics of one, two or threerelated polar body genomes; and comparing the one or more geneticcharacteristics of one, two or three related polar body genomes with oneor more one or more genetic characteristics of a related diploid genome.In some embodiments, the one or more one or more genetic characteristicsof a related diploid genome are already determined and/or known, or aredetermined by sequencing and/or haplotyping, for example.

In illustrative embodiments, one or more methods include determining oneor more genetic characteristics of one or more related female germ linegenomes by determining one or more genetic characteristics of three ofthe related polar body genomes, and through a comparative process,determining the one or more genetic characteristics of the fourthrelated female germ line haploid genome. In illustrative embodiments,one or more methods include determining one or more geneticcharacteristics of one or more related female germ line genomes bydetermining one or more genetic characteristics of two of the relatedpolar body genomes, and through a comparative process, at leastpartially determining one or more of the one or more geneticcharacteristics of the related female germ line diploid genome. In someillustrative embodiments, the comparative process is a subtractiveprocess, where the one or more genetic characteristics of the two orthree related polar body genomes are compared with the one or moregenetic characteristics of the related diploid genomes.

In some embodiments, determining, optionally destructively, one or moregenetic characteristics of one or more related polar body genomesincludes determining one or more genetic characteristics of one or morerelated diploid genomes, of optionally three related polar body genomes,of optionally two related polar body genomes, and/or of optionally onerelated polar body genome.

In some embodiments, determining one or more genetic characteristics ofone or more related polar body genomes includes amplifying, optionallydestructively, one or more nucleic acid sequences of the one or morerelated polar body genomes and/or one or more related diploid genomes.In some embodiments, amplifying one or more nucleic acid sequences ofthe one or more related polar body genomes includes amplifying in vitroand/or in situ the one or more nucleic acid sequences of the one or morerelated polar body genomes.

In some embodiments, determining one or more genetic characteristics ofone or more related polar body genomes includes sequencing, optionallydestructively, one or more nucleic acids of the one or more relatedpolar body genomes and/or one or more related diploid genomes. In someembodiments, sequencing one or more nucleic acids of the one or morerelated polar body genomes includes sequencing in vitro and/or in situthe one or more nucleic acids of the one or more related polar bodygenomes.

In some embodiments, determining one or more genetic characteristics ofone or more related polar body genomes includes co-localizing, binding,and/or hybridizing, optionally destructively, one or more probes and/orone or more molecular markers to one or more nucleic acid sequences ofthe one or more related polar body genomes and/or one or more relateddiploid genomes. In some embodiments, co-localizing, binding, and/orhybridizing one or more probes and/or one or more molecular markers toone or more nucleic acid sequences of the one or more related polar bodygenomes includes hybridizing the one or more probes and/or molecularmarkers, optionally nucleic acid sequence specific probes, in vitroand/or in situ to the one or more nucleic acid sequences of the one ormore related polar body genomes.

In some embodiments, determining the one or more genetic characteristicsof the one or more related polar body genomes includes detecting, and/oridentifying optionally destructively, one or more nucleic acid sequencesof the one or more related polar body genomes and/or one or more relateddiploid genomes. In some embodiments, detecting and/or identifying oneor more nucleic acid sequences of the one or more related polar bodygenomes includes detecting and/or identifying one or more markers of theone or more nucleic acid sequences, and/or one or more probes and/or oneor more molecular markers co-localized, bound, and/or hybridized to theone or more nucleic acid sequences of the one or more related polar bodygenomes.

In some embodiments, determining one or more genetic characteristics ofone or more related polar body genomes includes receiving datarepresentative of the one or more genetic characteristics and/or one ormore nucleic acid sequences of the one or more related polar bodygenomes and/or one or more related diploid genomes. In some embodiments,receiving data includes receiving data from one or more internal and/orexternal sources and/or inputs.

In some embodiments, determining one or more genetic characteristics ofone or more related polar body genomes includes analyzing the one ormore genetic characteristics of the one or more related polar bodygenomes and/or one or more related diploid genomes. In some embodiments,determining one or more genetic characteristics of one or more relatedfemale germ line genomes at least partially based on the geneticcharacteristics of one or more of the one or more related polar bodygenomes includes deducing and/or identifying the one or more geneticcharacteristics of the one or more related female germ line genomes atleast partially based on the genetic characteristics of one or more ofthe one or more related polar body genomes and/or one or more relateddiploid genomes.

In some embodiments, one or more methods include sequencing one or morenucleic acids of the one or more related polar body genomes and/or oneor more related diploid genomes. In some embodiments, one or moremethods include co-localizing, binding, and/or hybridizing one or moremolecular markers and/or one or more probes with one or more nucleicacid sequences of the one or more related polar body genomes and/or oneor more related diploid genomes. In some embodiments, one or moremethods include detecting and/or identifying one or more nucleic acidsequences of the one or more related polar body genomes and/or one ormore related diploid genomes.

In some embodiments, one or more methods include analyzing the one ormore genetic characteristics of the one or more related polar bodygenomes and/or one or more related diploid genomes. In some embodiments,analyzing the one or more genetic characteristics of the one or morerelated polar body genomes includes analyzing one or more singlenucleotide polymorphisms, one or more chromosomes, one or moremethylation patterns, and/or one or more nucleic acid sequences of theone or more related polar body genomes and/or one or more relateddiploid genomes.

In some embodiments, analyzing the one or more genetic characteristicsof the one or more related polar body genomes includes comparing the oneor more genetic characteristics of the one or more related polar bodygenomes with one or more reference genetic characteristics and/or one ormore target genetic characteristics, and/or with a weighted combinationof one or more reference genetic characteristics and/or one or moretarget genetic characteristics. In some embodiments, one or more methodsinclude determining and/or selecting one or more reference geneticcharacteristics and/or one or more target genetic characteristics atleast partially based on one or more genetic characteristics of one ormore male genomes optionally one or more male germ line genomes and/orone or more female genomes optionally female germ line genomes.

In some embodiments, comparing the one or more genetic characteristicsof the one or more related female germ line genomes with one or morereference genetic characteristics and/or one or more target geneticcharacteristics includes selecting for and/or against one or morerelated female germ line genomes at least partially based on thepresence of one or more reference genetic characteristics and/or the oneor more target genetic characteristics, and/or the presence of aweighted combination of one or more reference genetic characteristicsand/or the one or more target genetic characteristics.

In some embodiments, selecting one or more related female germ linegenomes includes selecting, sorting, and/or separating one or morerelated female germ line genomes at least partially based on one or moregenetic characteristics of one or more male germ line haploid genomes.In some embodiments, one or more methods include separating the selectedone or more related female germ line genomes. In some embodiments, oneor more methods include co-localizing one or more of the one or morerelated female germ line genomes with one or more male germ line haploidgenomes. In some embodiments, one or more methods include providing oneor more of the one or more related female germ line genomes to one ormore male germ line haploid genomes.

In one aspect, the disclosure is drawn to one or more compositionscomprising one or more germ line genomes. In some embodiments, one ormore compositions are generated using one or more of the methodsdescribed herein and/or one or more of the apparatus described herein,and/or one of the systems described herein.

In some embodiments, one or more compositions include one or morecontainers including one or more male germ line haploid genomes, the oneor more male germ line haploid genomes selected at least partially basedon one or more genetic characteristics of the one or more male germ linehaploid genomes, the one or more genetic characteristics of the one ormore male germ line haploid genomes selected at least partially based onone or more genetic characteristics of one or more female germ linegenomes.

In some embodiments, one or more compositions include one or morecontainers including one or more at least partially decondensed malegerm line haploid genomes, the one or more male germ line haploidgenomes selected at least partially based on one or more geneticcharacteristics of the one or more male germ line haploid genomes. Insome embodiments, one or more male germ line haploid genomes areselected at least partially based on one or more genetic characteristicsof the one or more male germ line haploid genomes, the one or moregenetic characteristics of the one or more male germ line haploidgenomes selected at least partially based on one or more geneticcharacteristics of one or more female germ line genomes. In someembodiments, one or more of the at least partially decondensed male germline haploid genomes is at least partially recondensed.

In some embodiments, one or more compositions include one or morecontainers including one or more related spermatid genomes, the one ormore male germ line haploid genomes selected at least partially based onone or more genetic characteristics of one or more related spermatidgenomes. In some embodiments, the one or more related spermatid genomesare selected at least partially based on one or more of the one or moregenetic characteristics of the one or more related spermatid genomes,the one or more genetic characteristics of the one or more relatedspermatid genomes selected at least partially based on one or moregenetic characteristics of one or more female germ line genomes.

In some embodiments, one or more compositions include one or morecontainers including one or more female germ line haploid genomes, theone or more female germ line haploid genomes selected at least partiallybased on one or more genetic characteristics of one or more relatedpolar body genomes. In some embodiments, the one or more female germline haploid genomes are selected at least partially based on the one ormore genetic characteristics of the one or more related polar bodygenomes, the one or more genetic characteristics of the one or morerelated polar body genomes selected at least partially based on one ormore genetic characteristics of one or more male germ line genomes. Insome embodiments, the one or more male germ line genomes are one or moremale haploid germ line genomes.

In some embodiments, one or more compositions include one or morecontainers including one or more female germ line haploid genomes, theone or more female germ line haploid genomes selected at least partiallybased on one or more genetic characteristics of one or more male germline genomes. In some embodiments, the one or more male germ linegenomes are one or more male haploid germ line genomes.

In one aspect, the disclosure is drawn to one or more apparatus forselecting one or more germ line genomes at least partially based on oneor more genetic characteristics of one or more germ line genomes. Insome embodiments, one or more of the methods described herein may beperformed on one or more apparatus. In some embodiments, one or more ofthe compositions described herein may be created using one or moreapparatus. In some embodiments, one or more system methods may beperformed on one or more apparatus, and/or one or more apparatus mayinclude one or more system or computing devices described herein.

FIG. 15 shows a schematic 400 of an illustrative apparatus 410 in whichembodiments may be implemented. The apparatus 410 is optionally operablefor characterizing, monitoring, detecting, hybridizing, amplifying,sequencing, identifying, analyzing, and/or determining one or moregenetic characteristics of one or more germ line genomes, as well asoptionally selecting, separating, sorting, providing, and/orco-localizing one or more germ line genomes. The apparatus mayoptionally be, or include, one or more units including, but not limitedto, one or more characterization units 419, one or more sourcing units420, one or more hybridization units 422, one or more monitoring units424, one or more controller units 426, one or more computing units 428,one or more sequencing units 430, one or more amplifying units 432,and/or one or more decondensing units 434. In some embodiments, one ormore of the units may be internal or external to the apparatus. In someembodiments, one or more of the units may be part of or separate fromthe apparatus.

In some embodiments, one or more characterization units 419 are operableto characterize one or more genetic characteristics of one or moregenomes. In some embodiments, one or more characterization units 419include and/or are the same as, one or more of one or more sourcingunits 420, one or more hybridization units 422, one or more monitoringunits 424, one or more controller units 426, one or more computing units428, one or more sequencing units 430, one or more amplifying units 432,and/or one or more decondensing units 434.

In some embodiments, one or more apparatus 410 further includes one ormore fluid flows. In some embodiments, the one or more fluid flowsconnect and/or allow the transfer of one or more germ line genomes aswell as other components, including but not limited to probes andmolecular markers, among one or more of the optional one or more unitsof the apparatus 410. In some embodiments, the one or more fluid flowsare operable to provide, co-localize, remove and/or separate, optionallysequentially, one or more germ line genomes as well as other components.In some embodiments, the one or more fluid flows are operable toprovide, co-localize, remove and/or separate, optionally sequentially,one or more germ line genomes as well as other components at one or moreidentifiable time intervals.

In some embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or moremale germ line haploid genomes and one or more second sources of one ormore probes; one or more hybridization units 422 operable to co-localizeone or more of the one or more probes with one or more nucleic acids ofthe one or more male germ line haploid genomes; one or more monitoringunits 424 operable to detect one or more of the one or more probeshybridized to the one or more nucleic acids of the one or more male germline haploid genomes; and one or more controller units 426 operable toselect, sort, and/or separate one or more of the one or more male germline haploid genomes at least partially based on the detection of one ormore of the one or more probes hybridized to the one or more nucleicacids.

In some embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or moremale germ line haploid genomes and one or more second sources of one ormore probes; one or more hybridization units 422 operable to co-localizeone or more of the one or more probes with one or more nucleic acids ofthe one or more male germ line haploid genomes; one or more monitoringunits 424 operable to detect one or more of the one or more probeshybridized to the one or more nucleic acids of the one or more male germline haploid genomes; and one or more computing units 428 operable todetermine the one or more male germ line haploid genomes to select,sort, and/or separate at least partially based on the detection of oneor more of the one or more probes hybridized to the one or more nucleicacids.

In some embodiments, one or more apparatus 410 includes one or morefirst sources of one or more male germ line haploid genomes; one or moresecond sources of one or more probes; one or more monitors for detectingone or more of the one or more probes; one or more units for hybridizingone or more of the one or more probes with one or more nucleic acids ofthe one or more male germ line haploid genomes; and one or morecontrollers for selecting one or more of the one or more male germ linehaploid genomes at least partially based on the detection of one or moreof the one or more probes hybridized to the one or more nucleic acids.

In some embodiments, one or more apparatus 410 includes one or moredetecting units operable to identify one or more genetic characteristicsof one or more male germ line haploid genomes using one or more nucleicacid detecting molecules other than a polyamide or Hoechst; one or morefirst sourcing units containing one or more sources of one or more malegerm line haploid genomes; one or more second sourcing units containingone or more sources of the one or more nucleic acid detecting molecules;and one or more first controller units operable to select one or more ofthe one or more male germ line haploid genomes at least partially basedon the one or more genetic characteristics of the one or more male germline haploid genomes.

In some embodiments, one or more apparatus includes one or morecharacterization units operable to detect and/or identify one or moreprobes hybridized to one or more nucleic acid sequences of one or moremale germ line haploid genomes; and one or more controller unitsoperable to select, sort, and/or separate one or more of the one or moremale germ line haploid genomes at least partially based on the detectionand/or identification of one or more probes hybridized to one or morenucleic acid sequences. In some embodiments, one or more apparatusincludes one or more characterization units operable to detect and/oridentify one or more probes hybridized to one or more nucleic acidsequences of one or more male germ line haploid genomes; and one or morecomputing units operable to determine the one or more male germ linehaploid genomes to select, sort, and/or separate at least partiallybased on the detection and/or identification of one or more probeshybridized to one or more nucleic acid sequences.

In some embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or moremale germ line haploid genomes; one or more monitoring units 424operable to detect one or more genetic characteristics of the one ormore male germ line haploid genomes; one or more computing units 428operable to receive one or more inputs, the one or more inputs includingdata representative of one or more genetic characteristics of one ormore female germ line genomes; one or more controller units 426 operableto select, sort, and/or separate one or more of the one or more malegerm line haploid genomes at least partially based on the one or moregenetic characteristics of the one or more female germ line genomes. Insome embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or moremale germ line haploid genomes; one or more monitoring units 424operable to detect one or more genetic characteristics of the one ormore male germ line haploid genomes; one or more computing units 428operable to receive one or more inputs, the one or more inputs includingdata representative of one or more genetic characteristics of one ormore female germ line genomes; and operable to determine the one or moremale germ line haploid genomes to select, sort, and/or separate at leastpartially based on the one or more genetic characteristics of the one ormore female germ line genomes.

In some embodiments, one or more apparatus 410 includes one or morefirst sources of one or more male germ line haploid genomes; one or moremonitors for detecting one or more genetic characteristics of the one ormore male germ line haploid genomes; one or more units for receiving oneor more inputs, the one or more inputs including data representative ofone or more genetic characteristics of one or more female germ linegenomes; one or more controllers for selecting one or more of the one ormore male germ line haploid genomes at least partially based on the oneor more genetic characteristics of the one or more female germ linegenomes.

In some embodiments, one or more apparatus 410 includes one or morecharacterization units 419 operable to detect and/or identify one ormore genetic characteristics of one or more male germ line haploidgenomes; one or more computing units 428 operable to receive one or moreinputs, the one or more inputs including data representative of one ormore genetic characteristics of one or more female germ line genomes;and one or more controller units 426 operable to select, sort, and/orseparate one or more of the one or more male germ line haploid genomesat least partially based on the one or more genetic characteristics ofthe one or more female germ line genomes. In some embodiments, one ormore apparatus 410 includes one or more characterization units 419operable to detect and/or identify one or more genetic characteristicsof one or more male germ line haploid genomes; one or more computingunits 428 operable to receive one or more inputs, the one or more inputsincluding data representative of one or more genetic characteristics ofone or more female germ line genomes; and operable to determine the oneor more male germ line haploid genomes to select, sort, and/or separateat least partially based on the one or more genetic characteristics ofthe one or more female germ line genomes.

In some embodiments, one or more apparatus 410 includes one or morecomputing units 428 operable to receive one or more inputs, the one ormore inputs including data representative of one or more geneticcharacteristics of one or more female germ line genomes; and one or morecontroller units 426 operable to select, sort, and/or separate one ormore of the one or more male germ line haploid genomes at leastpartially based on the one or more genetic characteristics of the one ormore female germ line genomes. In some embodiments, one or moreapparatus 410 includes one or more computing units 428 operable toreceive one or more inputs, the one or more inputs including datarepresentative of one or more genetic characteristics of one or morefemale germ line genomes; and operable to determine the one or more malegerm line haploid genomes to select, sort, and/or separate at leastpartially based on the one or more genetic characteristics of the one ormore female germ line genomes.

In some embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or moremale germ line haploid genomes, the one or more male germ line haploidgenomes at least partially condensed; one or more decondensing units 434operable to at least partially or completely decondense the one or moremale germ line haploid genomes; one or more monitoring units 424operable to detect one or more genetic characteristics of the one ormore male germ line haploid genomes; and one or more controller units426 operable to select one or more of the one or more male germ linehaploid genomes at least partially based on the one or more geneticcharacteristics of the one or more male germ line haploid genomes. Insome embodiments, one or more apparatus 411 includes one or more firstsources of one or more male germ line haploid genomes, the one or moremale germ line haploid genomes at least partially condensed; one or moreunits for decondensing the one or more male germ line haploid genomes;one or more monitors for detecting one or more genetic characteristicsof the one or more male germ line haploid genomes; and one or morecontrollers for selecting one or more of the one or more male germ linehaploid genomes at least partially based on the one or more geneticcharacteristics of the one or more male germ line haploid genomes.

In some embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or morerelated spermatid genomes; one or more monitoring units 424 operable todetect one or more genetic characteristics of one or more of the one ormore related spermatid genomes; and one or more controller units 426operable to select, sort, and/or separate one or more of the one or morerelated spermatid genomes at least partially based on one or more of thegenetic characteristics of one or more of the one or more relatedspermatid genomes.

In some embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or morerelated spermatid genomes; one or more computing units 428 operable toreceive one or more inputs, the one or more inputs including datarepresentative of one or more characteristics of one or more of the oneor more related spermatid genomes; and one or more controller units 426operable to select, sort, and/or separate one or more of the one or morerelated spermatid genomes at least partially based on the one or moregenetic characteristics of one or more of the one or more relatedspermatid genomes.

In some embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or morerelated spermatid genomes; one or more computing units 428 operable toreceive one or more inputs, the one or more inputs including datarepresentative of one or more characteristics of one or more of the oneor more related spermatid genomes; and operable to determine the one ormore related spermatid genomes to select, sort, and/or separate at leastpartially based on the one or more genetic characteristics of one ormore of the one or more related spermatid genomes.

In some embodiments, one or more apparatus 410 includes one or morecharacterization units 419 operable to determine, detect, and/oridentify one or more genetic characteristics of one or more relatedspermatid genomes; and one or more controller units 426 operable toselect, sort, and/or separate one or more of the one or more relatedspermatid genomes at least partially based on the one or more geneticcharacteristics of one or more of the one or more related spermatidgenomes. In some embodiments, one or more apparatus 410 includes one ormore characterization units 419 operable to determine, detect, and/oridentify one or more genetic characteristics of one or more relatedspermatid genomes; and one or more computing units 428 operable todetermine the one or more related spermatid genomes to select, sort,and/or separate at least partially based on the one or more geneticcharacteristics of one or more of the one or more related spermatidgenomes.

In some embodiments, one or more apparatus 410 includes one or moresourcing units 420 including one or more first sources of one or morerelated polar body genomes; one or more monitoring units 424 operable todetect one or more genetic characteristics of one or more of the one ormore related polar body genomes; and one or more controller units 426operable to select, sort, and/or separate one or more of the one or morerelated polar body genomes at least partially based on one or more ofthe genetic characteristics of one or more of the one or more relatedpolar body genomes. In some embodiments, one or more apparatus 410includes one or more sourcing units 420 including one or more firstsources of one or more related polar body genomes; one or more computingunits 428 operable to receive one or more inputs, the one or more inputsincluding data representative of one or more characteristics of one ormore of the one or more related polar body genomes; and one or morecontroller units 426 operable to select, sort, and/or separate one ormore of the one or more related polar body genomes at least partiallybased on the one or more genetic characteristics of one or more of theone or more related polar body genomes. In some embodiments, one or moreapparatus 410 includes one or more sourcing units 420 including one ormore first sources of one or more related polar body genomes; one ormore computing units 428 operable to receive one or more inputs, the oneor more inputs including data representative of one or morecharacteristics of one or more of the one or more related polar bodygenomes; and operable to determine the one or more related polar bodygenomes to select, sort, and/or separate at least partially based on theone or more genetic characteristics of one or more of the one or morerelated polar body genomes.

FIG. 16 shows a schematic 400 of illustrative embodiments of theoptional apparatus 410 of FIG. 15, with specific illustrativeembodiments of one or more sourcing units 420, including, but notlimited to, unit 4200, unit 4201, unit 4202, unit 4203, unit 4204, andunit 4205. In some embodiments, one or more sourcing units 420 areinternal to the apparatus 410; in some embodiments, one or more sourcingunits are external to the apparatus 410. In some embodiments, one ormore sourcing units are part of, the same as, and/or included in one ormore characterization units 419, one or more of one or morehybridization units 422, one or more monitoring units 424, one or morecontroller units 426, one or more computing units 428, one or moresequencing units 430, one or more amplifying units 432, and/or one ormore decondensing units 434.

In some embodiments, one or more sourcing units include one or morefirst sources of one or more male germ line haploid genomes 4200 and/orone or more related spermatid genomes 4201, the one or more firstsources optionally positioned to provide the one or more male germ linehaploid genomes and/or related spermatid genomes, to one or more firstlocations, one or more first units, one or more monitoring units, one ormore controller units, one or more computing units, one or moresequencing units, and/or one or more hybridization units.

In some embodiments, one or more sourcing units 420 include one or moresecond sources of one or more probes 4202 and/or one or more molecularmarkers 4203, the one or more second sources optionally positioned toprovide the one or more probes to one or more second locations, one ormore first units, one or more monitoring units, one or more controllerunits, one or more computing units, one or more sequencing units, and/orone or more hybridization units.

In some embodiments, one or more sourcing units 420 include one or morethird sources of one or more female germ line genomes 4204 and/or one ormore related polar body genomes 4205, the one or more third sourcesoptionally positioned to provide the one or more female germ linegenomes and/or related polar body genomes to one or more thirdlocations, one or more first units, one or more monitoring units, one ormore controller units, one or more computing units, one or moresequencing units, and/or one or more hybridization units.

In some embodiments, one or more sourcing units 420 are operable toreceive one or more inputs, the one or more inputs optionally includingone or more of one or more female germ line genomes, one or more malegerm line genomes, one or more probes and/or one or more moleculemarkers. In some embodiments, one or more sourcing units 420 areoperable to provide one or more outputs, the one or more outputsoptionally including one or more of one or more female germ linegenomes, and/or one or more male germ line genomes. In some embodiments,the one or more male germ line genomes and/or the female germ linegenomes are one or more haploid germ line genomes. In some embodiments,one or more male germ line genomes are one or more spermatid genomes,optionally one or more related spermatid genomes. In some embodiments,one or more female germ line genomes are one or more polar body genomes,optionally one or more related polar body genomes, and/or optionally oneor more of one or more first polar body genomes or one or more secondpolar body genomes.

In some embodiments, one or more first locations are the same as one ormore second locations, and/or one or more third locations, andoptionally are included in one or more hybridization units 422, one ormore monitoring units 424, one or more controller units 426, one or morecomputing units 428, one or more sequencing units, 430, one or moreamplifying units 432, and/or one or more decondensing units 434. In someembodiments, one or more third locations, one or more second locationsand/or one or more first locations are the same location.

In some embodiments, the one or more male germ line haploid genomes areat least partially isolated from one or more spermatozoa, and/or arepart of one or more spermatozoa. In some embodiments, the one or moremale germ line haploid genomes are at least partially isolated from oneor more spermatids and/or are part of one or more spermatids. In someembodiments, the one or more male germ line haploid genomes are at leastpartially isolated from one or more spermatocytes and/or are part of oneor more spermatocytes. In some embodiments, the one or more male germline haploid genomes are at least partially condensed and/or arecondensed. In some embodiments, the one or more male germ line haploidgenomes are from one or more of animals, mammals, reptiles, birds orplants.

In some embodiments, one or more related spermatid genomes are part ofone or more related spermatids and/or are at least partially isolatedfrom one or more related spermatids. In some embodiments, one or morerelated spermatid genomes are from one or more of animals, mammals,reptiles, birds or plants.

In some embodiments, the one or more female germ line genomes are atleast partially isolated from one or more of one or more ova, one ormore oogonia, or one or more oocytes and/or are part of one or more ofone or more ova, one or more oogonia, or one or more oocytes. In someembodiments, one or more female germ line genomes are from one or moreof animals, mammals, reptiles, birds or plants.

In some embodiments, one or more related polar body genomes are part ofone or more related polar bodies and/or are at least partially isolatedfrom one or more related polar bodies. In some embodiments, one or morerelated polar body genomes are from one or more of animals, mammals,reptiles, birds or plants.

FIG. 17 shows a schematic 400 of illustrative embodiments of theoptional apparatus 410 of FIG. 15, with specific illustrativeembodiments of one or more hybridization units 422, including but notlimited to, unit 4220, unit 4222, unit 4224, and/or unit 4226. In someembodiments, one or more hybridization units 422 are internal to theapparatus 410; in some embodiments, one or more hybridization units 422are external to the apparatus 410. In some embodiments, one or morehybridization units 422 are part of the apparatus 410; in someembodiments, one or more hybridization units 422 are separate from theapparatus 410. In some embodiments, one or more hybridization units 422are part of, the same as, and/or included in one or more of one or morecharacterization units 419, one or more sourcing units 420, one or moremonitoring units 424, one or more controller units 426, one or morecomputing units 428, one or more sequencing units 430, one or moreamplifying units 432, and/or one or more decondensing units 434.

In some embodiments, one or more hybridization units 422 are operable todetect one or more probes hybridized to one or more nucleic acidsoptionally of one or more male germ line haploid genomes and/or of oneor more female germ line genomes. In some embodiments, one or more ofthe one or more hybridization units are operable to identify one or moreof the one or more probes hybridized to one or more nucleic acidsoptionally of one or more male germ line haploid genomes and/or one ormore female germ line genomes.

In some embodiments, one or more hybridization 422 units are operable tohybridize one or more probes with one or more nucleic acid sequences4220 optionally of the one or more male germ line haploid genomes and/orone or more female germ line genomes. In some embodiments, one or morehybridization units are operable to co-localize one or more probes withone or more nucleic acid sequences 4222 of one or more male germ linehaploid genomes and/or one or more female germ line genomes.

In some embodiments, one or more hybridization units 422 are operable todetect 4224, optionally destructively, one or more nucleic acidsequences of one or more genomes. In some embodiments, one or morehybridization units are operable to identify 4226, optionallydestructively, one or more nucleic acid sequences of one or moregenomes. In some embodiments, one or more hybridization units 422 areoperable to detect 4224, optionally destructively, one or more probeshybridized to one or more nucleic acids optionally of one or morerelated spermatid genomes and/or of one or more related polar bodygenomes. In some embodiments, one or more hybridization units areoperable to identify 4226, optionally destructively, one or more probeshybridized to one or more nucleic acids optionally of one or morerelated spermatid genomes and/or one or more related polar body genomes.

In some embodiments, one or more hybridization units 422 are operable tohybridize 4220, optionally destructively, one or more probes with one ormore nucleic acid sequences optionally of the one or more relatedspermatid genomes and/or one or more related polar body genomes. In someembodiments, one or more hybridization units are operable to co-localize4222, optionally destructively, one or more probes with one or morenucleic acids of one or more related spermatid genomes and/or one ormore polar body genomes.

FIG. 18 shows a schematic 400 of illustrative embodiments of theoptional apparatus 410 of FIG. 15, with specific illustrativeembodiments of one or more monitoring units 424, including but notlimited to, unit 4240, unit 4241, unit 4242, and/or unit 4243. In someembodiments, one or more monitoring units 424 are internal to theapparatus 410; in some embodiments, one or more monitoring units 424 areexternal to the apparatus 410. In some embodiments, one or moremonitoring units 424 are part of the apparatus 410; in some embodiments,one or more monitoring units 424 are separate from the apparatus 410. Insome embodiments, one or more monitoring units 424 are part of, the sameas, and/or included in one or more of one or more characterization units419, one or more sourcing units 420, one or more hybridization units422, one or more controller units 426, one or more computing units 428,one or more sequencing units 430, one or more amplifying units 432,and/or one or more decondensing units 434.

In some embodiments, one or more monitoring units 424 are operable todetect and/or identify one or more genetic characteristics 4250 of oneor more female germ line genomes and/or one or more male germ linehaploid genomes. In some embodiments, one or more monitoring units areoperable to detect and/or identify one or more nucleic acid sequences4251 of one or more male germ line haploid genomes and/or one or morefemale germ line genomes.

In some embodiments, one or more monitoring units 424 are operable todetect association with, binding, and/or hybridization of one or moreprobes 4254 and/or one or more molecular markers with one or morenucleic acids of one or more male germ line haploid genomes and/or oneor more female germ line genomes. In some embodiments, one or moremonitoring units 424 are operable to detect and/or identify one or moreprobes or one or more molecular markers associated with, bound, and/orhybridized to one or more nucleic acids 4252 of one or more male germline haploid genomes and/or one or more female germ line genomes.

In some embodiments, one or more monitoring units are operable to detectand/or identify, optionally destructively, optionally in situ, one ormore genetic characteristics 4250 and/or one or more nucleic acidsequences 4251 of one or more related spermatid genomes and/or one ormore related polar body genomes. In some embodiments, one or moremonitoring units are operable to detect and/or identify, optionallydestructively, optionally in situ, one or more markers of one or morenucleic acid sequences 4253 of one or more related spermatid genomesand/or one or more related polar body genomes. In some embodiments, oneor more monitoring units are operable to detect and/or identify,optionally destructively, optionally in situ, one or more probeshybridized to one or more nucleic acid sequences 4252 of one or morerelated spermatid genomes and/or one or more related polar body genomes.

In some embodiments, one or more monitoring units are operable toamplify 4241, optionally destructively, optionally in situ, one or morenucleic acid sequences of one or more genomes. In some embodiments, oneor more monitoring units are operable to sequence 4242, optionallydestructively, optionally in situ, one or more nucleic acid sequences ofone or more genomes. In some embodiments, one or more monitoring unitsare operable to hybridize 4243, optionally destructively, optionally insitu, one or more probes to one or more nucleic acid sequences of one ormore genomes.

In some embodiments, one or more monitoring units are operable toamplify 4241, optionally destructively, optionally in situ, one or morenucleic acid sequences of one or more related spermatid genomes and/orone or more related polar body genomes. In some embodiments, one or moremonitoring units are operable to sequence 4242, optionallydestructively, optionally in situ, one or more nucleic acid sequences ofone or more of the one or more related spermatid genomes and/or one ormore related polar body genomes. In some embodiments, one or moremonitoring units are operable to hybridize 4243, optionallydestructively, optionally in situ, one or more probes to one or morenucleic acid sequences of the one or more related spermatid genomesand/or one or more related polar body genomes.

FIG. 19 shows a schematic 400 of illustrative embodiments of theoptional apparatus 410 of FIG. 15, with specific illustrativeembodiments of one or more controller units 426, including but notlimited to, unit 4260, unit 4261, unit 4262, unit 4263 and/or unit 4264.In some embodiments, one or more controller units 426 are internal tothe apparatus 410; in some embodiments, one or more controller units 426are external to the apparatus 410. In some embodiments, one or morecontroller units 426 are part of, the same as, and/or included in one ormore of one or more characterization units 419, one or more sourcingunits 420, one or more hybridization units 422, one or more monitoringunits 424, one or more computing units 428, one or more sequencing units430, one or more amplifying units 432, and/or one or more decondensingunits 434.

In some embodiments, one or more controller units 426 are operable toselect 4260, separate 4261, and/or sort 4262 one or more of the one ormore male germ line haploid genomes at least partially based on the oneor more genetic characteristics of the one or more male germ linehaploid genomes and/or a weighted combination of one or more geneticcharacteristics of one or more male germ line haploid genomes. In someembodiments, one or more controller units are operable to select 4260,separate 4261, and/or sort 4262 one or more of the one or more male germline haploid genomes at least partially based on one or more geneticcharacteristics of one or more female germ line genomes and/or aweighted combination of one or more genetic characteristics of one ormore female germ line genomes. In some embodiments, one or morecontroller units are operable to select 4260, separate 4261, and/or sort4262 one or more of the one or more male germ line haploid genomes atleast partially based on one or more of one or more target geneticcharacteristics or one or more reference genetic characteristics and/ora weighted combination of one or more of one or more target geneticcharacteristics or one or more reference genetic characteristics.

In some embodiments, one or more of the one or more controller units 426are operable to select 4260, separate 4261, and/or sort 4262 one or moreof the one or more male germ line haploid genomes optionally at leastpartially based on the detection and/or identification of one or moreprobes and/or molecular markers associated with, bound, and/orhybridized to one or more nucleic acids optionally of one or more malegerm line haploid genomes and/or one or more female germ line genomes.

In some embodiments, one or more controller units 426 are operable toprovide 4263 one or more probes to the one or more male germ linehaploid genomes, and/or to provide 4263 one or more male germ linehaploid genomes to one or more of the one or more probes. In someembodiments, one or more controller units are operable to provide 4263one or more male germ line haploid genomes and/or one or more of the oneor more probes to one or more first locations and/or to one or morehybridization units.

In some embodiments, one or more controller units 426 are operable toco-localize 4264 one or more probes with the one or more male germ linehaploid genomes, and/or to co-localize 4264 one or more male germ linehaploid genomes with one or more of the one or more probes. In someembodiments, one or more controller units are operable to co-localize4264 one or more male germ line haploid genomes and/or one or more ofthe one or more probes at one or more first locations and/or at one ormore hybridization units.

In some embodiments, the one or more male germ line haploid genomes areone or more related spermatid genomes. In some embodiments, the one ormore female germ line genomes are one or more related polar bodygenomes, optionally one or more first polar body genomes and/or one ormore second polar body genomes.

FIG. 20 shows a schematic 400 of illustrative embodiments of theoptional apparatus 410 of FIG. 15, with specific illustrativeembodiments of one or more computing units 428, including but notlimited to, unit 4280, unit 4281, and/or unit 4282. In some embodiments,one or more computing units 428 are internal to the apparatus 410; insome embodiments, one or more computing units 428 are external to theapparatus 410. In some embodiments, one or more computing units 428 arepart of, the same as, and/or included in one or more of one or morecharacterization units 419, one or more sourcing units 420, one or morehybridization units 422, one or more monitoring units 424, one or morecontroller units 426, one or more sequencing units 430, one or moreamplifying units 432, and/or one or more decondensing units 434.

In some embodiments, one or more apparatus 410 further includes one ormore computing units 428 operable to determine one or more geneticcharacteristics 4280 of one or more genomes and/or a weighted analysisof one or more genetic characteristics of one or more genomes.

In some embodiments, one or more computing units 428 are operable todetermine one or more genetic characteristics and/or a weighted analysisof one or more genetic characteristics 4280 of one or more genomes,optionally one or more male germ line haploid genomes and/or one or morefemale germ line genomes, optionally at least partially based ondetection and/or identification of one or more of the one or more probeshybridized to the one or more nucleic acids of one or more of the one ormore male germ line haploid genomes. In some embodiments, one or morecomputing units are operable to determine one or more geneticcharacteristics and/or a weighted analysis of one or more geneticcharacteristics 4280 of one or more genomes, optionally one or more malegerm line haploid genomes and/or one or more female germ line genomes,optionally at least partially based on the detected one or more geneticcharacteristics of the one or more male germ line haploid genomes.

In some embodiments, one or more computing units 428 are operable todetermine one or more genetic characteristics and/or a weighted analysisof one or more genetic characteristics 4280 of one or more genomes,optionally one or more related spermatid genomes and/or one or morerelated polar body genomes, optionally at least partially based ondetection and/or identification of one or more of the one or more probesand/or one or more molecular markers associated with, bound, and/orhybridized to the one or more nucleic acids of one or more relatedgenomes. In some embodiments, one or more computing units are operableto determine one or more genetic characteristics and/or a weightedanalysis of one or more genetic characteristics 4280 of one or moregenomes, optionally one or more related spermatid genomes and/or one ormore related polar body genomes, optionally at least partially based onthe detected one or more genetic characteristics of the one or morerelated genomes.

In some embodiments, the one or more computing units 428 are operable todetermine one or more genomes to select, sort, and/or separate 4281 atleast partially based on one or more genetic characteristics of one ormore related genomes, and/or based on a weighted analysis of one or moregenetic characteristics of one or more related genomes 4291. In someembodiments, one or more related genomes are one or more relatedspermatid genomes and/or one or more related polar body genomes.

In some embodiments, the one or more computing units 428 are operable todetermine one or more genomes, optionally one or more male germ linehaploid genomes and/or one or more female germ line genomes, to select,sort, and/or separate 4281 at least partially based on one or moregenetic characteristics of one or more male genomes, optionally one ormore male germ line haploid genomes, and/or on a weighted analysis ofone or more genetic characteristics of one or more male genomes,optionally one or more male germ line haploid genomes 4292.

In some embodiments, one or more computing units are operable todetermine one or more genomes, optionally one or more male germ linehaploid genomes and/or one or more female germ line genomes, to select,sort, and/or separate 4281 at least partially based on one or moregenetic characteristics of one or more female genomes, optionally one ormore female germ line genomes, and/or a weighted analysis of one or moregenetic characteristics of one or more female genomes, optionally one ormore female germ line genomes 4293.

In some embodiments, one or more computing units 428 are operable todetermine one or more male genomes, optionally one or more male germline haploid genomes and/or one or more female germ line genomes, toselect, sort, and/or separate 4281 at least partially based on one ormore of one or more target genetic characteristics or one or morereference genetic characteristics and/or a weighted combination of oneor more of one or more target genetic characteristics 4294 or one ormore reference genetic characteristics 4295.

In some embodiments, one or more computing units 428 are operable toreceive one or more inputs 4282, the one or more inputs optionallyincluding data representative of one or more genetic characteristics4286 and/or one or more nucleic acid sequences 4287 of one or moregenomes, optionally one or more female germ line genomes and/or one ormore male germ line genomes. In some embodiments, the one or more femalegerm line genomes and/or the one or more male germ line genomes are oneor more haploid genomes. In some embodiments, one or more computingunits 428 are operable to receive one or more inputs 4282, the one ormore inputs optionally including data representative of one or more ofone or more target genetic characteristics and/or one or more referencegenetic characteristics 4285.

In some embodiments, the one or more male germ line haploid genomes areone or more related spermatid genomes 4291. In some embodiments, the oneor more female germ line genomes are one or more related genomes 4291,optionally one or more polar body genomes, optionally one or more firstpolar body genomes and/or one or more second polar body genomes.

Materials and reagents described in the Examples are commerciallyavailable, unless otherwise specified.

EXAMPLE 1

Mammalian Spermatozoa Selection Based on Nucleic Acid Hybridization withPeptide Nucleic Acid

Sperm cells from, for example, boar, bull, stallion or ram, arecollected using known animal husbandry methods including using agloved-hand, an artificial vagina, and/or electro-ejaculation methods asappropriate.

After collection, the semen is diluted with a species-specific buffer toextend the lifespan of the sperm outside the body (e.g. artificialinsemination buffer). Appropriate diluents provide energy and nutrients,buffering action for pH changes (e.g. due to lactic acid formation),protection from temperature shock (e.g. rapid cooling), maintain osmoticpressure, balance electrolytes, inhibit microorganism growth, as well asfacilitating dilution to an appropriate volume for hybridization andselection. For example, a 2.9% sodium citrate—egg yolk buffer may beused for cattle (see, e.g., J. Dairy Sci. (1941) 24:905), and aBeltsville Thaw Solution (BTS) may be used for boar sperm.

The DNA sequence of interest is identified. Such DNA sequence can be,for example, a trait locus, a particular allele, or other DNA sequencetargeted for hybridization.

Based on the sequence of the DNA to be targeted, peptide nucleic acidsthat bind the target DNA sequence are designed and constructed followingthe procedures described, for example, by Eur. J. Hum. Genetics (2003)11:337-341; Mammalian Genome (2000) 11:384-391; Adv. in Genetics (2006)56:1-51; EMBO J. (2003) 22:6631-6641; Mammalian Genome (1999) 10:13-18;or Mol. Hum. Repro. (2004) 10:467-472). Alternatively, the peptidenucleic acids may be synthesized using an Applied Biosystems 3400 DNASynthesizer or an ABI 3900 Synthesizer, or using custom commercialservices.

Peptide nucleic acids (from, for example, Applied Biosystems) may beconjugated with various fluorescent dyes such as FITC, TRITC, and/orBODIPY® derivatives, for example, and/or quantum dots (see, e.g.,Histochem. Cell Biol. (2006) 125:451-456). BODIPY® dyes are membranesoluble, aiding penetration of probes (from, for example, MolecularProbes Inc.; described in, for example, U.S. Pat. No. 5,338,854 or U.S.Pat. No. 4,774,339). PNA probes are used at a final concentration ofabout 0.1 to about 100 μM depending on the cell concentration, amongother things.

Labeled or unlabeled peptide nucleic acids are added to diluted spermsamples under conditions to effect hybridization while minimizing theimpact on motility and/or viability. In some instances, peptide nucleicacid probes with fluorescent tags may readily penetrate the cells,travel to the nucleus, and bind nuclear DNA. Optionally, cellpenetration is facilitated by methods known in the art includingelectroporating, chemically shocking (e.g. using glycerol and/or DMSO),liposome-encapsulating, micro-injecting, DEAE-dextran-mediatedtransferring, co-precipitating with calcium phosphate, and/or addingcell-permeation enhancing solutions such as mild surfactants and/orDMSO.

Hybridization incubations may range from about 30 minutes to about 24hours or about 144 hours or longer, depending on the ease of uptake intothe cell nucleus and target binding. Hybridization temperatures mayrange from the thermotropic phase transition temperature of themembranes of the sperm, to room temperature (approximately 23° C.), toless than about 30° C., or to less than about 39° C.

Cells with fluorescently labeled peptide nucleic acids that hybridizedto target nucleic acids are identified by detection of their emittedfluorescence using conventional methods. Following hybridization, cellsare sorted, using for example flow cytometry or microfluorometry, basedon differences in quantitative and/or qualitative fluorescence toproduce subpopulations enriched or depleted in cells with one or moretarget sequences. Cells may also be sorted using fluorescent microscopy.Methods for effecting flow cytometry separations while minimizing theimpact on cell motility and/or viability are known in the art (e.g. U.S.Pat. No. 5,135,759, or U.S. Pat. No. 5,985,216), and appropriate systemshave been described herein, and in WO 03/020877, for example.

EXAMPLE 2 Mammalian Spermatozoa Nuclei Selection based on Nucleic AcidHybridization with Peptide Nucleic Acid

Methods of isolating sperm nuclei are known in the art (see, e.g., Hum.Reprod. (2005) 20:2784-2789). Semen is washed three times bycentrifugation at 1620 g for 10 minutes in, for example, 50 mmol/LTris-HCl, pH 7.2 and 0.15 mol/L NaCl (10× sample volume). Sperm pelletsare resuspended in, for example, 2.6 ml of the same buffer containing 1%SDS, incubated for 15 minutes at room temperature, and sonicated sixtimes for 15 seconds each at 200 W using, for example, a Bransonsonifier cell disrupter, model W 140 (Branson Sonic Power Co.,Plainview, N.Y.). Sonicated cell solutions are centrifuged at 3500 g for1 hour through a 1.1 mol/L sucrose in 50 mmol/L Tris-HCl, pH 7.2gradient. Pellets are washed twice by centrifugation at 1620 g for 10minutes in, for example, 50 mmol/L Tris-HCl, pH 7.2. Lack ofcontamination of the nuclear fraction may be assessed by microscopicexamination, for example.

PNAs are designed and constructed using methods and materials describedherein or known in the art. Hybridization of the PNA is induced usingthe methods and materials described herein or known in the art.

Following hybridization, nuclei are sorted, using for example flowcytometry or microfluorometry, based on differences in quantitativeand/or qualitative fluorescence to produce subpopulations enriched ordepleted in nuclei with one or more target sequences. Alternatively,nuclei may be sorted using fluorescent microscopy. Methods for effectingflow cytometry separations while minimizing the impact on nucleiviability are known in the art (e.g. U.S. Pat. No. 5,135,759 or U.S.Pat. No. 5,985,216), and appropriate systems have been described herein,and, for example, in WO 03/020877.

EXAMPLE 3 Decondensation and Nucleic Acid-Based Selection of MammalianSpermatozoa

Semen samples are obtained using methods known in the art and/ordescribed herein. Semen may be allowed to liquefy at room temperaturefor approximately 30 min to 3 hours.

Semen solutions are demembranated, for example by diluting 1:10 in ademembranating solution pre-warmed to approximately 37° C., or otherappropriate temperature based, for example, on the body temperature ofthe species from which the sperm is recovered. Demembranating solutionsare known in the art (see, e.g., J. Exp. Zoology (1999) 284:789-797),and can be modified to achieve the desired extent of demembranation byaltering, for example, the concentration of Triton X-100 (speciallypurified for membrane research, available from, for example,Boehringer-Mannhein, Germany) in the solution from approximately 0.01%,0.015%, 0.017%, 0.02%, to 0.022%, for example. During demembranation,samples may be stirred for 20 seconds, and allowed to sit unstirred for25 seconds.

Demembranated semen samples are decondensed, for example by diluting1:10 with decondensing solution pre-warmed to approximately 37° C. (orother appropriate temperature as discussed above), stirred briefly, andthen allowed to incubate at 37° C. for approximately 30 seconds, 5minutes, 10 minutes or 15 minutes depending on the species and extent ofdecondensation desired. Decondensation solutions are known in the art(see, e.g., J. Exp. Zoology (1999) 284:789-797), and may include 24 mMpotassium glutamate, 192 mM sucrose, 1.2 mM MgSO₄, 19.2 mM Hepes(N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid), 5.8 mM EDTA(ethylene diamine tetraacetic acid), 2.9 mM DTT (dithiothreitol, SigmaD-0632), 48 μM cAMP (adenosine 3′:5′-cyclic monophosphate; SigmaA-6885), and 4.03 USP units/ml heparin (sodium salt grade 1: fromporcine intestinal mucosa, Sigma), pH 7.8.

Demembranated and/or decondensed sperm samples may be diluted 1:10 inreactivating solution pre-warmed to approximately 37° C. (or otherappropriate temperature as discussed above), stirred briefly, and thenallowed to incubate at 37° C. for a few minutes. Reactivating solutionsare known in the art (e.g. J. Exp. Zoology (1999) 284:789-797), and mayinclude 5 mM adenosine 5′-triphosphate (ATP, Sigma A-5394) and 2.5 mMMgSO₄.

Sperm demembranation, decondensation, and/or reactivation can bemonitored using microscopic examination, for example.

Decondensed, and optionally reactivated, sperm may be exposed to one ormore nucleic acid binding solutions including polyamide, peptide nucleicacid, and/or oligonucleic acid probes under conditions to facilitatebinding and/or hybridization.

EXAMPLE 4 Decondensation and Nucleic Acid-Based Selection of MammalianSpermatozoa and Isolated Nuclei

Semen may be obtained by methods described herein and/or in the art.Semen samples are allowed to liquefy up to one hour prior tocapacitation or nuclei isolation.

Methods for capacitating semen samples are known in the art (see, e.g.,Hum. Reprod. (2005) 20:2784-2789). Semen samples are washed twice bycentrifugation at 300 g for 10 minutes in a 1:5 dilution of tubal fluidmedium (e.g. HTF; from, for example, Irvine Sceintific, Santa Ana,Calif.) supplemented with 0.3% bovine serum albumin (BSA). The spermpellet is overlaid with 1 ml fresh HTF with 2.6% BSA (HTF-26B) for 90minutes at about 37° C. (or other appropriate temperature for thespecies) in an atmosphere of 5% CO₂ in air.

Sperm nuclei then are isolated using methods known in the art, or asdescribed herein, for example in Example 2 above.

Methods of decondensing capacitated sperm and isolated nuclei are knownin the art (see, e.g., Hum. Reprod. (2005) 20:2784-2789). Sperm andisolated nuclei are incubated in HTF with 46 μmol/L Heparin and 10mmol/L glutathione (GSH) for approximately 15, 30 or 60 minutes at 37°C. (or other appropriate temperature for the species) in an atmosphereof 5% CO₂ in air. The extent of decondensation can be assessed byphase-contrast in an Olympus CH2 microscope at 400× magnification, forexample.

Decondensed sperm and/or isolated nuclei can be exposed to one or morenucleic acid binding solutions including, for example, polyamide,peptide nucleic acid, and/or oligonucleic acid probes under conditionsto facilitate binding and/or hybridization, as appropriate.

EXAMPLE 5 Decondensation of Mammalian Spermatozoa

Methods for decondensing mammalian sperm are known in the art (see,e.g., Theriogenology (2005) 63:783-794). Frozen or fresh sperm (frome.g. boar, bovine) may be incubated in Dulbecco's phosphate bufferedsaline (DPBS; Life Technologies) supplemented with 0.1% polyvinylalcohol (PVA) and 5 mM DTT for approximately 50 minutes. Otherappropriate buffers may be used, and the final DTT concentration varieddepending on the species of the sperm. Sperm are washed three timesbefore fertilization by centrifugation at 400 g for 5 minutes in 2 mlDPBS-PVA without 5 mM DTT.

EXAMPLE 6 Recondensation of Selected Mammalian Spermatozoa and IsolatedNuclei

Methods for recondensing DNA are known in the art and include incubationwith protamine in a low ionic strength buffer (see, e.g., J. Biol. Chem.(2004) 279:20088-20095). Partially and/or completely decondensed spermand/or isolated nuclei can be partially and/or completely recondensed byincubation with protamine in a low ionic strength buffer.

Protamine can be isolated from sperm cells (e.g. bull protamine frombull sperm cells, or species specific to the sperm and/or isolatednuclei) by methods known in the art (see, e.g., J. Biol. Chem. (2004)279:20088-20095). Isolated sperm cell chromatin is solubilized in 2.6 Murea, 1.1 M NaCl, 0.9 M guanidine hydrochloride (GuCl), and 150 mM2-mercaptoethanol, and DNA is precipitated from the solution withconcentrated HCl. The protamine solution is dialyzed against 10 mM HCl,and the protamine is precipitated with trichloroacetic acid, washed inacetone, and dissolved in dH₂O.

Solubilized protamine is filter-sterilized using, for example, AmiconUltrafree-MC centrifugal filters with 0.22 μm pore diameter (Millipore).Partially or completely decondensed sperm and/or isolated nuclei areincubated in a solution including approximately 2.25 μM protamine, 10 mMsodium cacodylate, and 100 μM EDTA (pH 7.5) for approximately 10minutes, 30 minutes, one hour, two hours, to at least three hours at 37°C. (or other appropriate temperature for the species) in an atmosphereof 5% CO₂ in air.

EXAMPLE 7 Mammalian Female Reproductive Cell and/or Isolated NucleiSelection Based on Nucleic Acid Hybridization and/or Binding

Female reproductive cells, including oocytes, ova, and/or polar bodies,from, for example, cows, sows, ewes, and mares are collected using knownanimal husbandry methods including, for example, super-ovulation, invitro production, and collection at slaughter. Mice, for example, may besuperovulated by consecutive injections of eCG (5 IU) and hCG (5 IU) 48hours apart. About 14 hours following hCG injections, oocyte-cumuluscomplexes are released from oviducts into Hepes-CZB. Cumulus cells canbe dispersed by 5 minutes treatment with 0.1% bovine testicularhyaluronidase (300 USP units/mg; from, for example, ICN Pharmaceuticals,Costa Mesa, Calif.) in Hepes-CZB (see, e.g., Biol. Reprod. (1998)59:100-104).

After collection, female reproductive cells are cultured and/ormaintained in a variety of balanced salt solutions (e.g. TC199, M16,NCSU23) known in the art at appropriate temperatures, for example onesresembling the body temperature the species from which the cell wasisolated (e.g. mice at 37° C., pig at 39° C.). Cumulus-free mice oocytescan be kept in CZB at 37.5° C. under 5% CO₂ in air. Appropriatesolutions and temperatures extend the length of cell viability andfunction and may be modified as appropriate (see, e.g., J. Cell. Biol.(1986) 102:568).

Methods of designing and constructing probes to bind and/or hybridize totarget DNA sequences such as those indicative of a particular allele,trait locus, or other feature of interest are known in the art anddescribed herein. Probes may include peptide nucleic acids, polyamides,and/or oligonucleotides, among others, and may be tagged with one ormore tags known in the art and/or described herein.

Methods of imaging molecules in living cells and isolated cell nucleiare known in the art and described herein (see, e.g., Histochem. CellBiol. (2006) 125:451-456; Biochem. Biophys. Res. Commun. (2006)344:772-779; or Nature (2004) 5:856-862). One approach is to usequenched probes that fluoresce only when hybridized/bound to the targetnucleic acid sequence (see, e.g., Trends in Biotech. (2005) 23:225-230;or Curr. Organic Chem. (2006) 10:491-518).

Probes are provided to the nucleus, using for example, mild membranepermeabilization, microinjection, and/or probes amenable to uptake, suchas polyamides and peptide nucleic acids.

Following hybridization, cells and/or nuclei are sorted, using forexample flow cytometry or microfluorometry, based on differences inquantitative and/or qualitative fluorescence to produce subpopulationsenriched or depleted in cells and/or nuclei with one or more targetsequences. Alternatively, cells and/or nuclei can be sorted usingfluorescent microscopy. Methods for effecting flow cytometry separationswhile minimizing the impact on cells and/or nuclei viability are knownin the art (see, e.g., U.S. Pat. No. 5,135,759, or U.S. Pat. No.5,985,216), and appropriate systems have been described herein, and inWO 03/020877, for example.

EXAMPLE 8 Fertilization Using Polar Body Genomes

Female reproductive cells, including oocytes, ova, and/or polar bodies,from, for example, cows, sows, ewes, and mares are collected, culturedand maintained using methods described above in Example 7 or known inthe art.

Methods for enucleating recipient oocytes are known in the art (see,e.g., Biol. Reprod. (1998) 59:100-104). Enucleation of mice matureoocytes is performed using, for example, Hepes-CZB containing 5 μg/mlcytocholasin B (25° C. for 10 minutes). Oocytes held by a pipette arerotated until detection of a small, translucent ooplasmic spot—thelocation of metaphase II chromosomes. The zona pellucida is drilled withan enucleation pipette (approx. 10 μm inner diameter) by applying a fewpiezo pulses, and its tip is advanced until it reaches the translucentspot identified above. The translucent spot (and metaphase chromosomes)are drawn into the pipette gently, without breaking the plasma membrane,and pulled away from the oocyte until a stretched cytoplasmic bridgebreaks off. Success of enucleation may be assessed using Hoechst 33342staining.

Methods for transferring first polar bodies into enucleated oocytes areknown in the art (see, e.g., Biol. Reprod. (1998) 59:100-104). The zonapellucida of oocytes with live polar bodies (assessed according to, forexample, Live/Dead FertiLight; Molecular Probes, Inc. Eugene Oreg.) aredrilled into with a piezo-driven injection pipette. The plasma membraneof the polar body may be broken when sucking into the pipette. Theentire contents are injected into an enucleated oocyte, and areincubated in CZB for 2 hours at 37.5° C. under CO₂ in air prior tofertilization.

Methods for transferring second polar bodies into enucleated oocytesand/or nucleated zygotes are known in the art (see, e.g., J. Reprod.Fertility (1997) 110:263-266). Second polar bodies and female pronucleimay be removed from zygotes through the zonae pellucidae usingmicromanipulators under an inverted microscope with Nomarski optics, forexample. The second polar body is inserted into the perivitelline spaceof a recipient zygote with one pronucleus, and placed in a drop (10 μl)of fusion medium (300 mmol/L mannitol, 0.05 mmol/L CaCl₂, 0.1 mmol/LMgSO₄, 5 mg/ml polyvinylpyrrolidone) between the electrodes of acircular electrofusion chamber (from, for example, Shimadzu, Kyoto). Thewidth and depth of the electrode gap are 0.5 and 2.0 mm, respectively,and electrofusion is induced by applying 20 V/cm AC for 30 seconds, 3000V/cm DC for 10 μs, and 20 C/cm AC for 90 seconds, consecutively.

EXAMPLE 9 Selection of Ova Using First Polar Body and/or Second PolarBody Genetic Information

First and/or second polar bodies from oocytes are obtained using methodsknown in the art (e.g. Biol. Reprod. (1998) 59:100-104; J. Reprod.Fertility (1997) 110:263-266; Reproductive BioMedicine Online (2003)6:403-409; Mol. Hum. Reprod. (1999) 5:89-95). Oviductal oocytes may becollected from mice, for example, between 13 and 17 hours after hCGinjection, and the viability of the first polar body assessed (as above,for example). The second polar body may be extruded followingparthenogenic activation or fertilization.

Genetic analysis of the polar bodies is performed using methods known inthe art (see, e.g., Mol. Hum. Reprod. (1999) 5:89-95; Fertility andSterility (2002) 78:543-549; J. Assisted Reprod & Genetics (1998) 15:253-257; Prenat. Diagn. (2000) 20:1067-1071; Reprod. BioMed. OnLine(2002) 4:183-196; Prenat. Giagn. (2002) 21:767-780; or Mol. Cell.Endocrinol. (2001) 183:S47-S49). Based on the information gathered fromgenetic analysis of one or more of the polar bodies, and compared withthe genetic information of diploid cells, the genetic information of thehaploid ova can be determined. The desired ovum can be selected andelectrofused, for example, with a selected male pronuclei.

EXAMPLE 10 Selection of Spermatids and/or at Least Partially IsolatedSpermatid Nuclei

Spermatids from mature male mammals are isolated using methods known inthe art (see, e.g., Development (1995) 121:2397-2405). Seminiferoustubules isolated from a mature male mouse testis are placed in 1 ml ofcold (4-10° C.) 0.9% NaCl containing 1% (W/v) polyvinyl pyrrolidone(PVP, Mr 360×10³, ICN), and are cut into minute pieces. The seminiferoustubule suspension is mixed thoroughly with repeated pipettings with 2 mlcold PVP-saline (0.9% NaCl, 12% (w/v) PVP) to release spermatozoa,spermatids, and other reproductive cells. Cells can be identified indroplets on a Petrie dish, for example, covered with mineral oil. Cellscan be maintained at approximately 16-17° C. for several hours (e.g.three hours) during this process. Round spermatids can be recognized bytheir small size and centrally located chromatin mass.

Spermatid clones that are connected by stable cytoplamic bridges (orring canals) are identified and isolated using methods known in the art(see, e.g., Mol. Biol. Cell (2003) 14:2768-2780; or Histochem. CellBiol. (1997) 108:77-81).

Seminiferous vesicles are dissected free from the interstitial tissue ina Petrie dish containing phosphate-buffered saline solution, pH 7.4. Thetransillumination pattern may be identified under stereomicroscope, forexample, and tubules at stages I-IV of the cycle are selected and cutinto approximately 0.5 mm to 1 mm segments. The cells within the tubulescan be extruded by lowering a cover slip (20×20 mm), for example, overthe tubule allowing wicking of excess fluid to create a slightlyflattened monolayer (under 40× phase-contrast optics). The spermatidclones are separated, and binding and/or hybridization procedures areperformed on one, two, three, and/or four of the spermatids of a givenclone using methods described herein and/or known in the art.

The hybridization/binding patterns of the probes to the nucleic acidsequences of the individual spermatid clones are compared with the knownsequence or binding/hybridization pattern for diploid cells of the donororganism. Through a process of comparison and elimination, the predictedidentity of the nucleic acid sequences in a spermatid clone can bedetermined, and the desired spermatid selected.

EXAMPLE 11 Fertilization Using Spermatids and/or at Least PartiallyIsolated Spermatid Nuclei

Oocytes are fertilized with spermatids and/or isolated nuclei usingmethods that are known in the art (see, e.g., Development (1995)121:2397-2405). Whole spermatids are sucked into an injection pipette(4-10 μm internal diameter) that is attached to a Piezo electric pipettedriving unit (e.g. Model PMM-10, Prima Meat Packers, Tsuchiura, Japan);partially isolated nuclei can be obtained by drawing spermatids in andout of 4 μm internal diameter injection pipettes. The zona pellucida ofa mature unfertilized oocyte is drilled and the oolemma is broken byapplying Piezo pulses. The entire spermatid, with or without an intactplasma membrane, or the at least partially isolated nucleus, is expelledinto the ooplasm, and the pipette tip is gently withdrawn.

In one aspect, the disclosure is drawn to one or more methods comprisingreceiving a first input associated with a first possible dataset, thefirst possible dataset including data representative of one or moretarget genetic characteristics, wherein at least one of the one or moretarget genetic characteristics is a genetic characteristic other thansex chromosome identity; and determining parameters for selecting one ormore reproductive components based on the first possible dataset. Insome embodiments, the one or more methods comprise receiving a firstinput associated with a first possible dataset, the first possibledataset including data representative of one or more target geneticcharacteristics, wherein at least one of the one or more target geneticcharacteristics is a non-gender-specific genetic characteristic, or is agenetic characteristic other than gender. One or more of these methodsmay be used as part of one or more methods for selecting one or moregerm line genomes at least partially based on one or more geneticcharacteristics of one or more of the one or more germ line genomesand/or implemented on one or more apparatus 410 for selecting one ormore germ line genomes at least partially based on one or more geneticcharacteristics of one or more of the one or more germ line genomes.

FIG. 1, FIG. 2, and FIG. 3 show operational flow 100, operational flow600, and operational flow 700, respectively, representing illustrativeembodiments of operations related to determining parameters forselecting one or more reproductive components based on the firstpossible dataset. In FIG. 1, FIG. 2, and FIG. 3, and in the followingfigures that include various illustrative embodiments of operationalflows, discussion and explanation may be provided with respect toapparatus and methods described herein, and/or with respect to otherexamples and contexts. The operational flows may also be executed in avariety of other contexts and environments, and or in modified versionsof those described herein. In addition, although some of the operationalflows are presented in sequence, the various operations may be performedin various repetitions, concurrently, and/or in other orders than thosethat are illustrated.

After a start operation, the operational flow 100 moves to a receivingoperation 110, receiving a first input associated with a first possibledataset, the first possible dataset including data representative of oneor more target genetic characteristics, wherein at least one of the oneor more target genetic characteristics is a genetic characteristic otherthan sex chromosome identity. After a start operation, the operationalflow 600 moves to a receiving operation 610, receiving a first inputassociated with a first possible dataset, the first possible datasetincluding data representative of one or more target geneticcharacteristics, wherein at least one of the one or more target geneticcharacteristics is a non-gender-specific genetic characteristic. After astart operation, the operational flow 700 moves to a receiving operation710, receiving a first input associated with a first possible dataset,the first possible dataset including data representative of one or moretarget genetic characteristics, wherein at least one of the one or moretarget genetic characteristics is a genetic characteristic other thangender.

The operational flow 100 optionally moves to an accessing operation 210,accessing the first possible dataset in response to the first input. Forexample, data representative of one or more target geneticcharacteristics may be accessed.

The operational flow 100 optionally moves to a generating operation 310,generating the first possible dataset in response to the first input.For example, data representative of one or more target geneticcharacteristics may be generated.

The operational flow 100 optionally moves to a determining operation410, determining a graphical illustration of the first possible dataset.For example, data representative of one or more target geneticcharacteristics may be graphically represented.

Then, the operational flow 100 moves to a determining operation 510,determining parameters for selecting one or more reproductive componentsbased on a first possible dataset. For example, one or more parametersmay include, but are not limited to one or more target geneticcharacteristics and/or one or more genetic characteristics of one ormore reproductive components.

One or more of operations 110 (and/or 610 and/or 710) through 510 may beperformed or repeated, as appropriate under the circumstances, prior toan end operation.

Operations 110 to 510 may be performed with respect to a digitalrepresentation (e.g. digital data) of, for example, data representativeof one or more target genetic characteristics. The logic may accept adigital or analog (for conversion into digital) representation of aninput and/or provide a digitally-encoded representation of a graphicalillustration, where the input may be implemented and/or accessed locallyor remotely.

Operations 110 to 510 may be performed related to either a local or aremote storage of the digital data, or to another type of transmissionof the digital data. In addition to inputting, accessing querying,recalling, calculating, determining or otherwise obtaining the digitaldata, operations may be performed related to storing, assigning,associating, displaying or otherwise archiving the digital data to amemory, including for example, sending and/or receiving a transmissionof the digital data from a remote memory. Accordingly, any suchoperations may involve elements including at least an operator (e.g.human or computer) directing the operation, a transmitting computer,and/or receiving computer, and should be understood to occur in theUnited States as long as at least one of these elements resides in theUnited States.

FIG. 4 illustrates optional embodiments of the operational flow 100 ofFIG. 1, and analogous embodiments of the operational flow 100 of FIG. 2and/or FIG. 3 are expressly envisioned. FIG. 4 shows illustrativeembodiments of the receiving operation 110, receiving a first inputassociated with a first possible dataset, the first possible datasetincluding data representative of one or more target geneticcharacteristics, wherein at least one or more one or more target geneticcharacteristics is a genetic characteristic other than sex chromosomeidentity, including operations receiving types of inputs and data entryand may include at least one additional operation. Receiving operationsmay optionally include, but are not limited to, operation 1100,operation 1101, operation 1102, operation 1103, operation 1104,operation 1105, operation 1106, operation 1107, operation 1108,operation 1109, operation 1110, operation 1111, operation 1112,operation 1113, and/or operation 1114.

At the optional operation 1100, receiving a first input associated witha first possible dataset comprises receiving the first input associatedwith the first possible dataset, the first input including datarepresentative of one or more of the one or more target geneticcharacteristics.

In some embodiments, one or more of the one or more target geneticcharacteristics are selected from the group consisting of geneticattributes, single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, geneticdiseases, chromosomal abnormalities, genetic mutations, inversions,deletions, duplications, recombinations, chromosomes, nucleic acidsequences, genes, protein coding sequences, introns, exons, regulatorysequences, intergenic sequences, mitochondrial nucleic acid sequences,mitochondria, telomeres, telomere repeats, telomere lengths, centromererepeats, centromeres, methylation pattern, and epigenetic elements. Insome embodiments, one or more of the genetic attributes include one ormore of one or more physical attributes, one or more psychologicalattributes, or one or more mental attributes.

In some embodiments, one or more of the one or more physical attributesare selected from the group consisting of characteristics associatedwith vision, strength, flexibility, speed, coordination, gait,lactation, fertility, weight, pelt, skin, body type, skeleto-muscular,longevity, and intelligence. In some embodiments, one or more of the oneor more physical attributes are selected from the group consisting ofcharacteristics associated with hair, eyes, height, weight, skin, fur,fleece, and wool. In some embodiments, one or more of the one or morephysical attributes are selected from the group consisting ofcharacteristics associated with hair pattern, hair color, eye color, eyesight, bone length, bone density, skin color, fur thickness, fur color,fur texture, fleece color, fleece thickness, wool thickness, and woolcolor. In some embodiments, one or more of the one or more physicalattributes include disposition.

At the optional operation 1101, receiving a first input associated witha first possible dataset comprises receiving a first input associatedwith the first possible dataset, the first input including datarepresentative of one or more of the one or more target geneticcharacteristics of one or more of one or more genomes, one or morechromosomes, and/or one or more nucleic acids.

At the optional operation 1102, receiving a first input associated witha first possible dataset comprises receiving a first input associatedwith the first possible dataset, the first input including datarepresentative of one or more of the one or more target geneticcharacteristics of one or more of one or more mitochondrial genomes,and/or one or more telomeres.

At the optional operation 1103, receiving a first input associated witha first possible dataset comprises receiving a first input associatedwith the first possible dataset, the first input including datarepresentative of one or more of the one or more target geneticcharacteristics of one or more of one or more somatic cells, one or moregerm line cells, one or more zygotes, one or more diploid cells, one ormore haploid cells, and/or one or more reproductive cells. In someembodiments, the first input includes data representative of one or moreof the one or more target genetic characteristics of one or more of oneor more sperm, one or more spermatids, one or more spermatogonia, one ormore primary spermatocytes, or one or more secondary spermatocytes. Insome embodiments, the first input includes data representative of one ormore genetic characteristics of one or more of one or more ova, one ormore first polar bodies, or one or more second polar bodies.

At the optional operation 1104, receiving a first input associated witha first possible dataset comprises receiving a first input associatedwith the first possible dataset, the first input associated withdetermining one or more of the one or more target geneticcharacteristics. In some embodiments, the one or more target geneticcharacteristics are selected from the group consisting of geneticattributes, single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, geneticdiseases, chromosomal abnormalities, genetic mutations, inversions,deletions, duplications, recombinations, chromosomes, nucleic acidsequences, genes, protein coding sequences, introns, exons, regulatorysequences, intergenic sequences, mitochondrial nucleic acid sequences,mitochondria, telomeres, telomere repeats, telomere lengths, centromererepeats, centromeres, methylation pattern, and epigenetic elements.

At the optional operation 1105 and/or 1106, receiving a first inputassociated with a first possible dataset comprises receiving a firstdata entry associated with the first possible dataset, the first dataentry optionally including data representative of one or more of the oneor more target genetic characteristics. In some embodiments, the one ormore target genetic characteristics selected from the group consistingof genetic attributes, single nucleotide polymorphisms, haplotypes,allelic markers, alleles, disease markers, genetic abnormalities,genetic diseases, chromosomal abnormalities, genetic mutations,inversions, deletions, duplications, recombinations, chromosomes,nucleic acid sequences, genes, protein coding sequences, introns, exons,regulatory sequences, intergenic sequences, mitochondrial nucleic acidsequences, mitochondria, telomeres, telomere repeats, telomere lengths,centromere repeats, centromeres, methylation pattern, and epigeneticelements.

At the optional operation 1107 and/or 1108, receiving a first inputassociated with a first possible dataset comprises receiving a firstdata entry from a graphical user interface, optionally from at least onesubmission element of a graphical user interface, and optionally atleast partially identifying one or more elements of the first possibledataset.

At the optional operation 1109 and/or 1110 and/or 1111 and/or 1112and/or 1113, receiving a first input associated with a first possibledataset comprises receiving a first data entry at least partiallyidentifying one or more elements of the first possible dataset, one ormore of the one or more elements optionally including datarepresentative of one or more genetic characteristics. In someembodiments, one or more of the one or more elements including datarepresentative of one or more genetic characteristics selected from thegroup consisting of single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, chromosomalabnormalities, genetic mutations, inversions, deletions, duplications,recombinations, chromosomes, nucleic acid sequences, genes, proteincoding sequences, introns, exons, regulatory sequences, intergenicsequences, mitochondrial nucleic acid sequences, mitochondria,telomeres, telomere repeats, telomere lengths, centromere repeats,centromeres, methylation pattern, and epigenetic elements.

In some embodiments, one or more of the one or more elements optionallyincluding data representative of one or more of one or more genomes, oneor more chromosomes, and/or one or more nucleic acid sequences. In someembodiments, one or more of the one or more elements optionallyincluding data representative of one or more of one or moremitochondrial genomes and/or one or more telomeres. In some embodiments,one or more of the one or more elements optionally including datarepresentative of one or more of one or more somatic cells, one or moregerm line cells, one or more nuclei, one or more diploid cells, one ormore haploid cells, or one or more reproductive cells. In someembodiments, one or more of the one or more elements optionallyincluding data representative of one or more of one or more sperm, oneor more spermatids, one or more spermatogonia, one or more primaryspermatocytes, or one or more secondary spermatocytes. In someembodiments, one or more of the one or more elements optionallyincluding data representative of one or more of one or more ova, one ormore first polar bodies, or one or more second polar bodies.

At the optional operation 1114, receiving a first input associated witha first possible dataset comprises receiving a first data entry at leastpartially identifying one or more of the one or more target geneticcharacteristics. In some embodiments, one or more of the one or moretarget genetic characteristics selected from the group consisting ofgenetic attributes, single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, geneticdiseases, chromosomal abnormalities, genetic mutations, inversions,deletions, duplications, recombinations, chromosomes, nucleic acidsequences, genes, protein coding sequences, introns, exons, regulatorysequences, intergenic sequences, mitochondrial nucleic acid sequences,mitochondria, telomeres, telomere repeats, telomere lengths, centromererepeats, centromeres, methylation pattern, and epigenetic elements.

FIG. 6 illustrates optional embodiments of the operational flow 100 ofFIG. 1. FIG. 6 shows illustrative embodiments of the optional accessingoperation 210, including operations accessing the first possible datasetin response to the first input, and may include at least one additionaloperation. Accessing operations may optionally include, but are notlimited to, operation 2100, operation 2101, operation 2102, operation2103, operation 2104, operation 2105, operation 2106, operation 2107,operation 2108, operation 2109, operation 2110, operation 2111,operation 2112, operation 2113, operation 2114, and/or operation 2115.

At the optional operation 2100, accessing the first possible dataset inresponse to the first input comprises accessing the first possibledataset in response to the first input, the first input including datarepresentative of one or more of the one or more target geneticcharacteristics. In some embodiments, one or more of the one or moretarget genetic characteristics are selected from the group consisting ofone or more genetic attributes, single nucleotide polymorphisms,haplotypes, allelic markers, alleles, disease markers, geneticabnormalities, genetic diseases, chromosomal abnormalities, geneticmutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 2101, accessing the first possible dataset inresponse to the first input comprises accessing the first possibledataset from within a first database associated with a plurality ofgenetic characteristics. In some embodiments, one or more of the one ormore genetic characteristics selected from the group consisting ofsingle nucleotide polymorphisms, haplotypes, allelic markers, alleles,disease markers, genetic abnormalities, chromosomal abnormalities,genetic mutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 2102 and/or operation 2104, accessing thefirst possible dataset in response to the first input comprisesaccessing the first possible dataset by associating and/or correlatingand/or corresponding data representative of one or more of the one ormore target genetic characteristics with one or more elements of thefirst possible dataset. In some embodiments, one or more of the one ormore target genetic characteristics are selected from the groupconsisting of genetic attributes, single nucleotide polymorphisms,haplotypes, allelic markers, alleles, disease markers, geneticabnormalities, genetic diseases, chromosomal abnormalities, geneticmutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements with the one or more elements of thefirst possible dataset.

At the optional operation 2103, accessing the first possible dataset inresponse to the first input comprises accessing the first possibledataset using a database management system engine that is configured toquery a first database to retrieve the first possible dataset therefrom.

At the optional operation 2105 and/or 2106, accessing the first possibledataset in response to the first input comprises accessing the firstpossible dataset as being associated and/or correlated and/orcorresponded with data representative of one or more of the one or moretarget genetic characteristics, based on one or more characterizationsstored in association with one or more elements of the first possibledataset, the one or more elements optionally including one or moregenetic characteristics.

At the optional operation 2107 and/or 2108, receiving a first inputassociated with a first possible dataset comprises receiving a firstrequest associated with the first possible dataset, the first requestoptionally selecting data representative of the one or more targetgenetic characteristics. In some embodiments, one or more of the one ormore target genetic characteristics are selected from the groupconsisting of one or more genetic attributes, single nucleotidepolymorphisms, haplotypes, allelic markers, alleles, disease markers,genetic abnormalities, genetic diseases, chromosomal abnormalities,genetic mutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 2109 and/or 2110 and/or 2111 and/or 2112and/or 2113, and/or 2114, and/or 2115, receiving a first inputassociated with a first possible dataset comprises receiving a firstrequest from a graphical user interface, optionally from at least onesubmission element of a graphical user interface, optionally at leastpartially identifying one or more elements of the first possible datasetand/or optionally selecting one or more elements of the first possibledataset and/or optionally providing instructions identifying and/ordetermining and/or specifying one or more of the one or more targetgenetic characteristics, and optionally providing at least one otherinstruction.

In some embodiments, one or more of the one or more target geneticcharacteristics are selected from the group consisting of one or moregenetic attributes, single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, geneticdiseases, chromosomal abnormalities, genetic mutations, inversions,deletions, duplications, recombinations, chromosomes, nucleic acidsequences, genes, protein coding sequences, introns, exons, regulatorysequences, intergenic sequences, mitochondrial nucleic acid sequences,mitochondria, telomeres, telomere repeats, telomere lengths, centromererepeats, centromeres, methylation pattern, and epigenetic elements.

FIG. 7 illustrates optional embodiments of the operational flow 100 ofFIG. 1. FIG. 7 shows illustrative embodiments of the optional generatingoperation 310, including operations generating the first possibledataset in response to the first input, and may include at least oneadditional operation. Generating operations may optionally include, butare not limited to, operation 3100, operation 3101, operation 3102,operation 3103, operation 3104, operation 3105, operation 3106,operation 3107, operation 3108, operation 3109, operation 3110,operation 3111, operation 3112, operation 3113, operation 3114,operation 3115, and/or operation 3116.

At the optional operation 3100, generating the first possible dataset inresponse to the first input comprises generating the first possibledataset in response to the first input, the first input including datarepresentative of one or more of one or more target geneticcharacteristics. In some embodiments, one or more of the one or moretarget genetic characteristics are selected from the group consisting ofone or more genetic attributes, single nucleotide polymorphisms,haplotypes, allelic markers, alleles, disease markers, geneticabnormalities, genetic diseases, chromosomal abnormalities, geneticmutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 3101, generating the first possible dataset inresponse to the first input comprises generating the first possibledataset from within a first database associated with a plurality ofgenetic characteristics. In some embodiments, one or more of the one ormore genetic characteristics are selected from the group consisting ofone or more single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, chromosomalabnormalities, genetic mutations, inversions, deletions, duplications,recombinations, chromosomes, nucleic acid sequences, genes, proteincoding sequences, introns, exons, regulatory sequences, intergenicsequences, mitochondrial nucleic acid sequences, mitochondria,telomeres, telomere repeats, telomere lengths, centromere repeats,centromeres, methylation pattern, and epigenetic elements.

At the optional operation 3102, generating the first possible dataset inresponse to the first input comprises generating the first possibledataset by associating data representative of one or more of the one ormore target genetic characteristics with one or more elements of thefirst possible dataset. In some embodiments, one or more of the one ormore target genetic characteristics are selected from the groupconsisting of one or more genetic attributes, single nucleotidepolymorphisms, haplotypes, allelic markers, alleles, disease markers,genetic abnormalities, genetic diseases, chromosomal abnormalities,genetic mutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 3103, generating the first possible dataset inresponse to the first input comprises generating the first possibledataset using a database management system engine that is configured toquery a first database to retrieve the first possible dataset therefrom.

At the optional operation 3104, generating the first possible dataset inresponse to the first input comprises generating the first possibledataset by corresponding data representative of one or more of the oneor more target genetic characteristics with one or more elements of thefirst possible dataset. In some embodiments, one or more of the one ormore target genetic characteristics are selected from the groupconsisting of one or more genetic attributes, single nucleotidepolymorphisms, haplotypes, allelic markers, alleles, disease markers,genetic abnormalities, genetic diseases, chromosomal abnormalities,genetic mutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 3105 and/or 3106, receiving a first inputassociated with a first possible dataset comprises receiving a firstrequest associated with the first possible dataset, the first requestoptionally selecting one or more of the one or more target geneticcharacteristics. In some embodiments, one or more of the one or moretarget genetic characteristics are selected from the group consisting ofone or more genetic attributes, single nucleotide polymorphisms,haplotypes, allelic markers, alleles, disease markers, geneticabnormalities, genetic diseases, chromosomal abnormalities, geneticmutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 3107 and/or 3108, receiving a first inputassociated with a first possible dataset comprises receiving a firstrequest from a graphical user interface, and optionally from at leastone submission element of a graphical user interface.

At the optional operation 3109 and/or 3110, receiving a first inputassociated with a first possible dataset comprises receiving a firstrequest, the first request at least partially identifying one or moreelements of the first possible dataset and/or optionally selecting oneor more elements of the first possible dataset and/or optionallyproviding instructions at least partially identifying one or moreelements of the first possible dataset.

At the optional operation 3111 and/or 3112, receiving a first inputassociated with a first possible dataset comprises receiving a firstrequest, the first request providing instructions at least partiallyidentifying one or more of the one or more target geneticcharacteristics and/or providing instructions for determining one ormore of the one or more target genetic characteristics. In someembodiments, one or more of the one or more target geneticcharacteristics are selected from the group consisting of one or moregenetic attributes, single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, geneticdiseases, chromosomal abnormalities, genetic mutations, inversions,deletions, duplications, recombinations, chromosomes, nucleic acidsequences, genes, protein coding sequences, introns, exons, regulatorysequences, intergenic sequences, mitochondrial nucleic acid sequences,mitochondria, telomeres, telomere repeats, telomere lengths, centromererepeats, centromeres, methylation pattern, and epigenetic elements.

At the optional operation 3113 and 3114, receiving a first inputassociated with a first possible dataset comprises receiving a firstrequest associated with the first possible dataset 3113, and generatingthe first possible dataset in response to the first request, the firstrequest optionally specifying one or more of the one or more targetgenetic characteristics and optionally at least one other instruction3114. In some embodiments, receiving a first input associated with afirst possible dataset comprises receiving a first request associatedwith the first possible dataset, the first request selecting and/ordetermining data representative of one or more of the one or more targetgenetic characteristics, and generating the first possible dataset inresponse to the first input.

In some embodiments, receiving a first input associated with a firstpossible dataset comprises receiving a first request from a graphicaluser interface, optionally from at least one submission element of agraphical user interface, optionally at least partially identifying oneor more elements of the first possible dataset, and optionally selectingone or more elements of the first possible dataset, and generating thefirst possible dataset in response to the first input. In someembodiments, receiving a first input associated with a first possibledataset comprises receiving a first request from at least one submissionelement of a graphical user interface, the first request providinginstructions identifying and/or determining data representative of oneor more of the one or more target genetic characteristics, andgenerating the first possible dataset in response to the first input.

At the optional operations 3115 and 3116, receiving a first inputassociated with a first possible dataset comprises receiving a firstrequest, the first request specifying data representative of one or moreof the one or more target genetic characteristics 3115; and generatingthe first possible dataset in response to the first request at leastpartially by performing an analysis of data representative of the one ormore target genetic characteristics 3116. In some embodiments, one ormore of the one or more target genetic characteristics are selected fromthe group consisting of one or more genetic attributes, singlenucleotide polymorphisms, haplotypes, allelic markers, alleles, diseasemarkers, genetic abnormalities, genetic diseases, chromosomalabnormalities, genetic mutations, inversions, deletions, duplications,recombinations, chromosomes, nucleic acid sequences, genes, proteincoding sequences, introns, exons, regulatory sequences, intergenicsequences, mitochondrial nucleic acid sequences, mitochondria,telomeres, telomere repeats, telomere lengths, centromere repeats,centromeres, methylation pattern, and epigenetic elements.

In some embodiments, receiving a first input associated with a firstpossible dataset comprises receiving a first request, the first requestspecifying data representative of one or more of the one or more targetgenetic characteristics, and generating the first possible dataset inresponse to the first request at least partially by performing ananalysis of data representative of one or more of one or more targetnucleic acid sequences and/or target haplotypes.

FIG. 8 and FIG. 9 illustrate optional embodiments of the operationalflow 100 of FIG. 1. FIG. 8 and FIG. 9 show illustrative embodiments ofthe optional determining operation 410, including operations determininga graphical illustration of the first possible dataset, and may includeat least one additional operation. Determining operations may optionallyinclude, but are not limited to, operation 4100, operation 4101,operation 4102, operation 4103, operation 4104, operation 4105,operation 4106, operation 4107, operation 4108, operation 4109,operation 4110, operation 4111, operation 4112, operation 4113,operation 4114, and/or operation 4115.

At the optional operation 4100, determining a graphical illustration ofthe first possible dataset comprises determining the graphicalillustration of the first possible dataset for inclusion in a displayelement of a graphical user interface.

At the operations 4101 and 4102, determining a graphical illustration ofthe first possible dataset comprises performing an analysis of one ormore elements of the first possible dataset to determine a firstpossible outcome 4101; and determining the graphical illustration basedon the analysis 4102.

At the optional operations 4103 and 4104, determining a graphicalillustration of the first possible dataset comprises performing ananalysis of one or more elements of the first possible dataset todetermine a first possible outcome, the first possible outcome includingone or more of a possible risk, a possible result, a possibleconsequence, a likelihood of success, or a cost 4103; and determiningthe graphical illustration based on the analysis 4104.

At the optional operations 4105 and 4106, determining a graphicalillustration of the first possible dataset comprises performing ananalysis of one or more elements of the first possible dataset todetermine a first possible outcome, the first possible outcome includingone or more of a predicted risk, a predicted result, a predictedconsequence, a predicted likelihood of success, or a predicted cost4105; and determining the graphical illustration based on the analysis4106.

At the optional operations 4107 and 4108, determining a graphicalillustration of the first possible dataset comprises performing ananalysis of one or more elements of the first possible dataset todetermine a first possible outcome, the first possible outcome includingone or more of a possible risk, a possible result, a possibleconsequence, a likelihood of success, or a cost 4107; and determiningthe graphical illustration including data representative of one or moreof the one or more target genetic characteristics in association with avisual indicator related to the first possible outcome 4108. In someembodiments, one or more of the one or more target geneticcharacteristics are selected from the group consisting of one or moregenetic attributes, single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, geneticdiseases, chromosomal abnormalities, genetic mutations, inversions,deletions, duplications, recombinations, chromosomes, nucleic acidsequences, genes, protein coding sequences, introns, exons, regulatorysequences, intergenic sequences, mitochondrial nucleic acid sequences,mitochondria, telomeres, telomere repeats, telomere lengths, centromererepeats, centromeres, methylation pattern, and epigenetic elements.

At the optional operations 4109 and 4110, determining a graphicalillustration of the first possible dataset comprises performing ananalysis of one or more elements of the first possible dataset todetermine a first possible outcome, the first possible outcome includingone or more of a predicted risk, a predicted result, a predictedconsequence, a predicted likelihood of success, or a predicted cost4109; and determining the graphical illustration including datarepresentative of one or more of the one or more target geneticcharacteristics in association with a visual indicator related to thefirst possible outcome 4110. In some embodiments, one or more of the oneor more target genetic characteristics are selected from the groupconsisting of one or more genetic attributes, single nucleotidepolymorphisms, haplotypes, allelic markers, alleles, disease markers,genetic abnormalities, genetic diseases, chromosomal abnormalities,genetic mutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 4111, determining a graphical illustration ofthe first possible dataset comprises determining a correlation between afirst possible outcome and a type or characteristic of a visualindicator used in the graphical illustration to represent the firstpossible outcome.

At the optional operations 4112, 4113, 4114, and/or 4115, determining agraphical illustration of the first possible dataset comprisesdetermining the graphical illustration of a first possible outcome basedon use of one or more of the one or more reproductive components 4112,the one or more reproductive components optionally including one or moregenetic characteristics 4113, optionally including one or more of one ormore genomes, one or more chromosomes, one or more nucleic acidsequences, one or more mitochondrial nucleic acid sequences, and/or oneor more telomeres and/or telomere lengths 4114, and/or optionallyincluding one or more of one or more somatic cells, one or more germline cells, one or more nuclei, one or more diploid cells, one or morehaploid cells, and/or one or more reproductive cells 4115.

In some embodiments, one or more of the one or more target geneticcharacteristics are selected from the group consisting of one or moregenetic attributes, single nucleotide polymorphisms, haplotypes, allelicmarkers, alleles, disease markers, genetic abnormalities, geneticdiseases, chromosomal abnormalities, genetic mutations, inversions,deletions, duplications, recombinations, chromosomes, nucleic acidsequences, genes, protein coding sequences, introns, exons, regulatorysequences, intergenic sequences, mitochondrial nucleic acid sequences,mitochondria, telomeres, telomere repeats, telomere lengths, centromererepeats, centromeres, methylation pattern, and epigenetic elements.

In some embodiments, one or more of the one or more reproductivecomponents include, but are not limited to, one or more of one or morespermatozoa, one or more spermatids, one or more spermatogonia, one ormore primary spermatocytes, and/or one or more secondary spermatocytes.In some embodiments, one or more of the one or more reproductivecomponents include, but are not limited to, one or more of one or moreova, one or more first polar bodies, and/or one or more second polarbodies.

FIG. 10 illustrates optional embodiments of the operational flow 100 ofFIG. 11. FIG. 18 shows illustrative embodiments of the determiningoperation 510, including operations determining parameters for selectingone or more reproductive components based on the first possible dataset,and may include at least one additional operation. Determiningoperations may optionally include, but are not limited to, operation5100, operation 5101, operation 5102, operation 5103, operation 5104,operation 5105, operation 5106, operation 5107, operation 5108,operation 5109, operation 5110, and/or operation 5111.

At the optional operation 5100 and/or 5101, determining parameters forselecting one or more reproductive components based on the firstpossible dataset comprises determining parameters for selecting one ormore reproductive components based on the first possible dataset, thefirst possible dataset including data representative of one or more ofthe one or more target genetic characteristics and/or weighting of oneor more target genetic characteristics. In some embodiments, one or moreof the one or more target genetic characteristics are selected from thegroup consisting of one or more genetic attributes, single nucleotidepolymorphisms, haplotypes, allelic markers, alleles, disease markers,genetic abnormalities, genetic diseases, chromosomal abnormalities,genetic mutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements.

At the optional operation 5102 and/or 5103, determining parameters forselecting one or more reproductive components based on the firstpossible dataset comprises determining parameters for selecting one ormore reproductive components based on the first possible dataset, thefirst possible dataset including data representative of one or more ofthe one or more genetic characteristics and/or weighting of one or moreof the one or more genetic characteristics. In some embodiments, one ormore of the one or more genetic characteristics are selected from thegroup consisting of one or more single nucleotide polymorphisms,haplotypes, allelic markers, alleles, disease markers, geneticabnormalities, chromosomal abnormalities, genetic mutations, inversions,deletions, duplications, recombinations, chromosomes, nucleic acidsequences, genes, protein coding sequences, introns, exons, regulatorysequences, intergenic sequences, mitochondrial nucleic acid sequences,mitochondria, telomeres, telomere repeats, telomere lengths, centromererepeats, centromeres, methylation pattern, and epigenetic elements.

At the optional operation 5104 and/or 5105 and/or 5106, determiningparameters for selecting one or more reproductive components based onthe first possible dataset comprises determining parameters forselecting one or more reproductive components based on the firstpossible dataset, the one or more reproductive components including oneor more genetic characteristics 5104, optionally including one or moreof one or more genomes, one or more chromosomes, one or more nucleicacid sequences, one or more mitochondrial nucleic acid sequences, and/orone or more telomeres and/or telomere lengths 5105, and/or optionallyincluding one or more of one or more somatic cells, one or more germline cells, one or more nuclei, one or more diploid cells, one or morehaploid cells, and/or one or more reproductive cells 5106.

In some embodiments, one or more of the one or more geneticcharacteristics are selected from the group consisting of singlenucleotide polymorphisms, haplotypes, allelic markers, alleles, diseasemarkers, genetic abnormalities, chromosomal abnormalities, geneticmutations, inversions, deletions, duplications, recombinations,chromosomes, nucleic acid sequences, genes, protein coding sequences,introns, exons, regulatory sequences, intergenic sequences,mitochondrial nucleic acid sequences, mitochondria, telomeres, telomererepeats, telomere lengths, centromere repeats, centromeres, methylationpattern, and epigenetic elements. In some embodiments, one or morereproductive components include, but are not limited to, one or more ofone or more sperm, one or more spermatids, one or more spermatogonia,one or more primary spermatocytes, one or more secondary spermatocytes,one or more ova, one or more first polar bodies, and/or one or moresecond polar bodies.

At the optional operations 5107 and 5108, determining parameters forselecting one or more reproductive components based on the firstpossible dataset comprises performing an analysis of one or moreelements of the first possible dataset 5107; and determining parametersfor selecting one or more reproductive components, based on the analysis5108.

At the optional operations 5109 and 5110, determining parameters forselecting one or more reproductive components based on the firstpossible dataset comprises performing an analysis of one or moreelements of the first possible dataset and at least one additionalinstruction 5109; and determining parameters for selecting the one ormore reproductive components, based on the analysis 5110.

At the optional operation 5111, determining parameters for selecting oneor more reproductive components based on the first possible datasetcomprises determining parameters for selecting one or more reproductivecomponents based on the first possible dataset, the parameters includingone or more predicted outcomes using one or more of the one or morereproductive components.

In some embodiments, determining parameters for selecting one or morereproductive components based on the first possible dataset comprisesdetermining parameters for selecting the one or more reproductivecomponents based on the first possible dataset, the parameters includingone or more predicted outcomes selected from the group consisting ofdata characteristic of one or more of predicted risk, predicted result,predicted consequence, predicted likelihood of success, and predictedcost and/or data characteristic of weighting of one or more of predictedrisk, predicted result, predicted consequence, predicted likelihood ofsuccess, and predicted cost. In some embodiments, determining parametersfor selecting the one or more reproductive components based on the firstpossible dataset comprises determining parameters for selecting the oneor more reproductive components based on the first possible dataset, theparameters including one or more predicted outcomes selected from thegroup consisting of data characteristic of one or more of a possiblerisk, a possible result, or a possible consequence and/or datacharacteristic of weighting of one or more of a possible risk, apossible result, or a possible consequence.

FIG. 11, FIG. 12, and/or FIG. 13 show a schematic of a partial view ofan illustrative computer program product 1700 that includes a computerprogram for executing a computer process on a computing device. Anillustrative embodiment of the example computer program product isprovided using a signal bearing medium 1702, and may include at leastone instruction of 1704, 1804, and/or 1904: one or more instructions forreceiving a first input associated with a first possible dataset 1704,one or more instructions for processing a first possible dataset 1804,and/or one or more instructions responsive to a first possible dataset1904, the first possible dataset including data representative of one ormore target genetic characteristics, wherein at least one of the one ormore target genetic characteristics is optionally a non-gender-specificgenetic characteristic, a genetic characteristic other than sexchromosome identity, and/or a genetic characteristic other than gender;one or more instructions for accessing the first possible dataset inresponse to the first input; one or more instructions for generating thefirst possible dataset in response to the first input; one or moreinstructions for determining a graphical illustration of the firstpossible dataset; or one or more instructions for determining parametersfor selecting one or more reproductive components based on the firstpossible dataset. The one or more instructions may be, for example,computer executable and/or logic implemented instructions. In someembodiments, the signal bearing medium 1702 of the one or more computerprogram 1700 products include a computer readable medium 1706, arecordable medium 1708, and/or a communications medium 1710.

FIG. 14 shows a schematic of an illustrative system 2000 in whichembodiments may be implemented. The system 2000 may include a computingsystem environment. The system 2000 also illustrates an operator and/orresearcher 104 using a device 2004 that is optionally shown as being incommunication with a computing device 2002 by way of an optionalcoupling 2006. The optional coupling may represent a local, wide area,or peer-to-peer network, or may represent a bus that is internal to acomputing device (e.g. in illustrative embodiments the computing device2002 is contained in whole or in part within the device 2004, one ormore apparatus 410, one or more characterization units 419, one or morecomputing units 428, one or more controller units 426, one or moremonitoring units 424, one or more hybridization units 422, one or moresequencing units 430, one or more amplifying units 432, and/or one ormore decondensing units 434). An optional storage medium 2008 may be anycomputer storage medium.

The computing device 2002 includes one or more computer executableinstructions 2010 that when executed on the computing device 2002 causethe computing device 2002 to receive the first input associated with thefirst possible dataset, the first possible dataset including datarepresentative of one or more target genetic characteristics, optionallywherein at least one of the one or more target genetic characteristicsis a genetic characteristic other than sex chromosome identity;optionally access the first possible dataset in response to the firstinput; optionally generate the first possible dataset in response thefirst input; optionally determine a graphical illustration of the firstpossible dataset; and determine parameters for selecting one or morereproductive components at least partially based on a first possibledataset. In some embodiments, at least one of the target geneticcharacteristics is a non-gender specific target characteristic, agenetic characteristic other than sex chromosome identity, and/or agenetic characteristic other than gender. In some illustrativeembodiments, the computing device 2002 may optionally be contained inwhole or in part within one or more units of an apparatus 410 of FIG. 15(e.g. one or more characterization units 419, one or more computingunits 428, one or more controller units 426, one or more monitoringunits 424, one or more hybridization units 422, one or more sequencingunits 430, one or more amplifying units 432, and/or one or moredecondensing units 434), or may optionally be contained in whole or inpart within the operator device 2004.

The system 2000 includes at least one computing device (e.g. 2004 and/or2002 and/or one or more computing units 428 of FIG. 15) on which thecomputer-executable instructions 2010 may be executed. For example, oneor more of the computing devices (e.g. 2002, 2004, 428) may execute theone or more computer executable instructions 2010 and output a resultand/or receive information from the operator 104 (optionally from one ormore apparatus 410, one or more characterization units 419, one or morecontroller units 426, one or more monitoring units 424, one or morehybridization units 422, one or more decondensing units 434, one or moresequencing units 430, and/or one or more amplifying units 432) on thesame or a different computing device (e.g. 2002, 2004, 428) and/oroutput a result and/or receive information from an apparatus 410, one ormore characterization units 419, one or more controller units 426, oneor more monitoring units 424, one or more hybridization units 422, oneor more decondensing units 434, one or more sequencing units 430, and/orone or more amplifying units 432 in order to perform and/or implementone or more of the techniques, processes, or methods described herein,or other techniques.

The computing device (e.g. 2002 and/or 2004 and/or 428) may include oneor more of a desktop computer, a workstation computer, a computingsystem comprised a cluster of processors, a networked computer, a tabletpersonal computer, a laptop computer, or a personal digital assistant,or any other suitable computing unit. In some embodiments, any one ofthe one or more computing devices (e.g. 2002 and/or 2004 and/or 428) maybe operable to communicate with a database to access the first possibledataset and/or subsequent datasets. In some embodiments, the computingdevice (e.g. 2002 and/or 2004 and/or 428) is operable to communicatewith the apparatus 410.

There is little distinction left between hardware and softwareimplementations of aspects of systems; the use of hardware or softwareis generally (but not always, in that in certain contexts the choicebetween hardware and software can become significant) a design choicerepresenting cost vs. efficiency tradeoffs. There are various vehiclesby which processes and/or systems and/or other technologies describedherein can be effected (e.g., hardware, software, and/or firmware), andthat the preferred vehicle will vary with the context in which theprocesses and/or systems and/or other technologies are deployed. Forexample, if an implementer determines that speed and accuracy areparamount, the implementer may opt for a mainly hardware and/or firmwarevehicle; if flexibility is paramount, the implementer may opt for amainly software implementation; or, yet again alternatively, theimplementer may opt for some combination of hardware, software, and/orfirmware.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples. Insofar as such block diagrams, flowcharts, and/orexamples contain one or more functions and/or operations, it will beunderstood by those within the art that each function and/or operationwithin such block diagrams, flowcharts, or examples can be implemented,individually and/or collectively, by a wide range of hardware, software,firmware, or virtually any combination thereof. In one embodiment,several portions of the subject matter described herein may beimplemented via Application Specific Integrated Circuits (ASICs), FieldProgrammable Gate Arrays (FPGAs), digital signal processors (DSPs), orother integrated formats. However, those skilled in the art willrecognize that some aspects of the embodiments disclosed herein, inwhole or in part, can be equivalently implemented in integratedcircuits, as one or more computer programs running on one or morecomputers (e.g., as one or more programs running on one or more computersystems), as one or more programs running on one or more processors(e.g., as one or more programs running on one or more microprocessors),as firmware, or as virtually any combination thereof, and that designingthe circuitry and/or writing the code for the software and or firmwarewould be well within the skill of one of skill in the art in light ofthis disclosure. In addition, those skilled in the art will appreciatethat the mechanisms of the subject matter described herein are capableof being distributed as a program product in a variety of forms, andthat an illustrative embodiment of the subject matter described hereinapplies regardless of the particular type of signal bearing medium usedto actually carry out the distribution. Examples of a signal bearingmedium include, but are not limited to, the following: a recordable typemedium such as a floppy disk, a hard disk drive, a Compact Disc (CD), aDigital Video Disk (DVD), a digital tape, a computer memory, etc.; and atransmission type medium such as a digital and/or an analogcommunication medium (e.g., a fiber optic cable, a waveguide, a wiredcommunications link, a wireless communication link, etc.).

Those skilled in the art will recognize that it is common within the artto describe devices and/or processes in the fashion set forth herein,and thereafter use engineering practices to integrate such describeddevices and/or processes into data processing systems. That is, at leasta portion of the devices and/or processes described herein can beintegrated into a data processing system via a reasonable amount ofexperimentation. Those having skill in the art will recognize that atypical data processing system generally includes one or more of asystem unit housing, a video display device, a memory such as volatileand non-volatile memory, processors such as microprocessors and digitalsignal processors, computational entities such as operating systems,drivers, graphical user interfaces, and applications programs, one ormore interaction devices, such as a touch pad or screen, and/or controlsystems including feedback loops and control motors (e.g., feedback forsensing position and/or velocity; control motors for moving and/oradjusting components and/or quantities). A typical data processingsystem may be implemented utilizing any suitable commercially availablecomponents, such as those typically found in datacomputing/communication and/or network computing/communication systems.

The herein described subject matter sometimes illustrates differentcomponents contained within, or connected with, different othercomponents. It is to be understood that such depicted architectures aremerely exemplary, and that in fact many other architectures can beimplemented which achieve the same functionality. In a conceptual sense,any arrangement of components to achieve the same functionality iseffectively “associated” such that the desired functionality isachieved. Hence, any two components herein combined to achieve aparticular functionality can be seen as “associated with” each othersuch that the desired functionality is achieved, irrespective ofarchitectures or intermedial components. Likewise, any two components soassociated can also be viewed as being “operably connected”, or“operably coupled”, to each other to achieve the desired functionality,and any two components capable of being so associated can also be viewedas being “operably couplable”, to each other to achieve the desiredfunctionality. Specific examples of operably couplable include but arenot limited to physically mateable and/or physically interactingcomponents and/or wirelessly interactable and/or wirelessly interactingcomponents and/or logically interacting and/or logically interactablecomponents.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations may be expressly set forth herein for sakeof clarity.

It will be understood by those within the art that, in general, termsused herein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art that if aspecific number of an introduced claim recitation is intended, such anintent will be explicitly recited in the claim, and in the absence ofsuch recitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to inventions containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to “at least one of A, B, and C, etc.” is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., “a system having at least one ofA, B, and C” would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to “at least one of A, B, or C, etc.” is used, ingeneral such a construction is intended in the sense one having skill inthe art would understand the convention (e.g., “a system having at leastone of A, B, or C” would include but not be limited to systems that haveA alone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). It will be furtherunderstood by those within the art that virtually any disjunctive wordand/or phrase presenting two or more alternative terms, whether in thedescription, claims, or drawings, should be understood to contemplatethe possibilities of including one of the terms, either of the terms, orboth terms. For example, the phrase “A or B” will be understood toinclude the possibilities of “A” or “B” or “A and B.”

All references cited herein, including but not limited to patents,patent applications, and non-patent literature, are hereby incorporatedby reference herein in their entirety.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

1. A method comprising: hybridizing one or more probes in vitro to oneor more nucleic acid sequences of one or more male germ line haploidgenomes; determining one or more genetic characteristics of the one ormore male germ line haploid genomes; and selecting one or more of theone or more male germ line haploid genomes based at least partially onone or more of the one or more genetic characteristics of the one ormore male germ line haploid genomes.
 2. The method of claim 1, whereinhybridizing one or more probes in vitro to one or more nucleic acidsequences of one or more male germ line haploid genomes comprises:hybridizing one or more nucleic acid sequence specific probes in vitroto the one or more nucleic acid sequences of the one or more male germline haploid genomes.
 3. The method of claim 1, wherein hybridizing oneor more probes in vitro to one or more nucleic acid sequences of one ormore male germ line haploid genomes comprises: hybridizing the one ormore probes selected from the group consisting of a protein nucleic acidand an oligonucleotide in vitro to the one or more nucleic acidsequences of the one or more male germ line haploid genomes.
 4. Themethod of claim 1, further comprising: removing one or more of the oneor more probes from one or more of the nucleic acid sequences of one ormore of the one or more male germ line haploid genomes.
 5. The method ofclaim 1, further comprising: separating one or more of the one or moreprobes from one or more of the nucleic acid sequences of one or more ofthe one or more male germ line haploid genomes.
 6. The method of claim1, further comprising: eliminating one or more of the one or more probesfrom one or more of the nucleic acid sequences of one or more of the oneor more male germ line haploid genomes.
 7. The method of claim 1,wherein determining one or more genetic characteristics of the one ormore male germ line haploid genomes is at least partially based ondetecting the hybridization of the one or more probes in vitro to theone or more nucleic acid sequences of the one or more male germ linehaploid genomes.
 8. The method of claim 1, further comprising: detectingthe hybridization of the one or more probes in vitro to the one or morenucleic acid sequences of the one or more male germ line haploidgenomes.
 9. The method of claim 8, wherein detecting the hybridizationof the one or more probes in vitro to the one or more nucleic acidsequences of the one or more male germ line haploid genomes comprises:detecting a marker of hybridization, the marker of hybridizationselected from the group consisting of quantum dots, molecular beacons,fluorescence, and FRET.
 10. The method of claim 1 , wherein the one ormore male germ line haploid genomes is at least partially condensed. 11.The method of claim 1, wherein the one or more male germ line haploidgenomes are part of one or more spermatozoa.
 12. The method of claim 1,wherein the one or more male germ line haploid genomes are at leastpartially isolated from one or more spermatozoa.
 13. The method of claim1, wherein the one or more male germ line haploid genomes are part ofone or more spermatids.
 14. The method of claim 1, wherein the one ormore male germ line haploid genomes are at least partially isolated fromone or more spermatids.
 15. The method of claim 1, wherein the one ormore genetic characteristics of the one or more male germ line haploidgenomes include one or more of one or more single nucleotidepolymorphisms, one or more chromosomal characteristics, one or moremethylation patterns, or one or more DNA sequences.
 16. The method ofclaim 1, wherein the one or more genetic characteristics of the one ormore male germ line haploid genomes include one or more of one or moremitochondrial nucleic acid sequences, one or more telomeric sequences,or one or more telomeric lengths.
 17. The method of claim 16, whereinthe one or more telomeric lengths are selected from the group consistingof a total genomic telomeric length, a telomeric length of one or moreends of one or more chromosomes, and a weighted combination of one ormore telomeric lengths of one or more ends of one or more chromosomes.18. The method of claim 1, wherein the one or more geneticcharacteristics of the one or more male germ line haploid genomesinclude a weighted combination of one or more of the one or more geneticcharacteristics.
 19. The method of claim 18, wherein the one or moregenetic characteristics of the one or more male germ line haploidgenomes include a weighted combination of one or more of one or moresingle nucleotide polymorphisms, one or more chromosomalcharacteristics, one or more methylation patterns, or one or more DNAsequences.
 20. The method of claim 1, wherein selecting one or more ofthe one or more male germ line haploid genomes is based at leastpartially on one or more target genetic characteristics.
 21. The methodof claim 1, further comprising: analyzing the one or more geneticcharacteristics of the one or more male germ line haploid genomes. 22.The method of claim 21, wherein analyzing the one or more geneticcharacteristics of the one or more male germ line haploid genomescomprises: comparing the one or more genetic characteristics of one ormore of the one or more male germ line haploid genomes with one or moreof one or more reference or one or more target genetic characteristics.23. The method of claim 22, further comprising: determining one or moreof the one or more reference or the one or more target geneticcharacteristics at least partially based on one or more geneticcharacteristics of one or more female germ line genomes.
 24. The methodof claim 22, further comprising: selecting one or more of the one ormore reference or the one or more target genetic characteristics atleast partially based on one or more genetic characteristics of one ormore female germ line genomes.
 25. The method of claim 22, wherein saidstep of comparing comprises: selecting for one or more of the one ormore male germ line haploid genomes having one or more of the one ormore reference or the one or more target genetic characteristics. 26.The method of claim 25, wherein said step of selecting for comprises:selecting for one or more of the one or more male germ line haploidgenomes having a weighted combination of one or more of the one or morereference or the one or more target genetic characteristics.
 27. Themethod of claim 22, wherein said step of comparing comprises: selectingagainst one or more of the one or more male germ line haploid genomeshaving one or more of the one or more reference or the one or moretarget genetic characteristics.
 28. The method of claim 27, wherein saidstep of selecting against comprises: selecting against one or more ofthe one or more male germ line haploid genomes having a weightedcombination of one or more of the one or more reference or the one ormore target genetic characteristics.
 29. The method of claim 22, whereinanalyzing the one or more genetic characteristics of the one or moremale germ line haploid genomes comprises: analyzing one or more of oneor more single nucleotide polymorphisms, one or more chromosomes, one ormore methylation patterns, or one or more nucleic acid sequences of theone or more male germ line haploid genomes.
 30. The method of claim 1,further comprising: selecting one or more of the one or more male germline haploid genomes based at least partially on one or more geneticcharacteristics of one or more female germ line genomes.
 31. The methodof claim 30, further comprising: determining one or more of the one ormore genetic characteristics of the one or more female germ linegenomes.
 32. The method of claim 30, further comprising: hybridizing oneor more probes in vitro to one or more nucleic acid sequences of the oneor more female germ line genomes; and determining one or more of the oneor more genetic characteristics of the one or more female germ linegenomes.
 33. The method of claim 30, wherein the one or more geneticcharacteristics of the one or more female germ line genomes include oneor more of one or more single nucleotide polymorphisms, one or morechromosomal characteristics, one or more methylation patterns, or one ormore DNA sequences.
 34. The method of claim 30, wherein the one or moregenetic characteristics of the one or more female germ line genomesinclude one or more of one or more mitochondrial nucleic acid sequences,one or more telomeric sequences, or one or more telomeric lengths. 35.The method of claim 34, wherein the one or more telomeric lengths areselected from the group consisting of a total genomic telomeric length,a telomeric length of one or more ends of one or more chromosomes, and aweighted combination of one or more telomeric lengths of one or moreends of one or more chromosomes.
 36. The method of claim 30, wherein theone or more genetic characteristics of the one or more female germ linegenomes include a weighted combination of one or more of one or moregenetic characteristics.
 37. The method of claim 36, wherein the one ormore genetic characteristics of the one or more female germ line genomesinclude a weighted combination of one or more of one or more singlenucleotide polymorphisms, one or more chromosomal characteristics, orone or more DNA sequences.
 38. The method of claim 30, wherein the oneor more female germ line genomes are one or more haploid genomes. 39.The method of claim 30, wherein the one or more female germ line genomesare part of one or more of one or more ova, one or more oogonia, or oneor more polar bodies.
 40. The method of claim 30, wherein the one ormore female germ line genomes are at least partially isolated from oneor more of one or more ova, one or more oogonia, or one or more polarbodies.
 41. The method of claim 30, further comprising: providing theselected one or more male germ line haploid genomes to the one or morefemale germ line genomes.
 42. The method of claim 30, furthercomprising: co-localizing the selected one or more male germ linehaploid genomes with the one or more female germ line genomes.
 43. Themethod of claim 1, further comprising: providing the selected one ormore male germ line haploid genomes to one or more female germ linegenomes.
 44. The method of claim 1, further comprising: co-localizingthe selected one or more male germ line haploid genomes with one or morefemale germ line genomes.
 45. A method comprising: detecting one or moregenetic characteristics of one or more male germ line haploid genomes atleast partially based on methods other than binding of one or morenucleic acids of the one or more male germ line haploid genomes with apolyamide or Hoechst; and selecting one or more of the one or more malegerm line haploid genomes based at least partially on the one or moregenetic characteristics of the one or more male germ line haploidgenomes.
 46. A method comprising: detecting one or more geneticcharacteristics of one or more male germ line haploid genomes at leastpartially based on sequence specific binding to one or more nucleicacids sequences, wherein the sequence specific binding is not polyamidesequence specific binding; and selecting one or more of the one or moremale germ line haploid genomes based at least partially on the one ormore genetic characteristics of the one or more male germ line haploidgenomes. 47-86. (canceled)